A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150 (MK-8150-002): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150 (MK-8150-002) (NCT01656408), a randomized phase 1 study. The primary outcome is Number of Participants With an Adverse Event (AE).

2. Clinical Question

These are related but distinct questions. A count of participants with an adverse event is a broad safety outcome, while the stated heart-rate hypothesis concerns a specific physiologic measure at specified times and in specified groups. The posted adverse-event counts cannot establish whether the heart-rate criterion was met, nor do they report changes in blood pressure, arterial stiffness, or pharmacokinetics. Although the record lists secondary outcome measures involving these types of measures, the posted results include only 28 secondary outcomes. The available information therefore supports a description of the adverse-event counts and their uncertainty, not a full answer to the study’s pharmacodynamic questions.

3. Trial Design

This was a randomized, double-blind, parallel-group phase 1 study of MK-8150, with placebo as a comparator. The registry record describes the study as a multiple-rising-dose evaluation of safety, tolerability, pharmacokinetics, and pharmacodynamics. It lists 103 enrolled participants and a completed status. The recorded study start was 2012-08-01, and the primary completion date was 2013-05-03.

The study used panels for different participant groups and regimens. Panels A through D were described as mild-to-moderate hypertension groups receiving MK-8150 or matching placebo once daily for 10 days. Panels E and F involved elderly participants and included a single dose, a wash-out of at least 5 days, and then once-daily dosing at a lower dose for 10 days. Panels G, I, and J used once-daily dosing for 28 days, with potential dose adjustments on Day 8, Day 15, and Day 22. Panel H was described as a two-period crossover with 10 consecutive days of treatment in each period and a minimum 3 weeks of wash-out between periods.

Panel-specific designs matter when interpreting the posted counts. The participant totals are small in several active-treatment panels, and the regimens and populations differ. The placebo result is pooled across Panels A through J. The registry notes that the 8 crossover Panel H participants appear in both the Panel H MK-8150 column and the pooled placebo column. Consequently, the treatment and placebo columns should not be treated as wholly independent groups in every respect. The record does not report detailed randomization procedures, allocation concealment, or a protocol-level explanation of how each panel contributed to each analysis.

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.

Only the first 6 of 10 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study drug

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.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With an Adverse Event (AE), measured over Up to 14 days after the last dose (Up to approximately 42 days, excluding pre-dose/screening period).

The posted primary endpoint is the number of participants with an adverse event, among participants who received at least one dose of study drug. An adverse event is defined broadly in the registry record as an unfavorable and unintended change in body structure, function, or chemistry temporally associated with study-drug use, whether or not considered related to treatment. Worsening of a preexisting condition is also included when it is temporally associated with study-drug use.

This endpoint is used to describe the number of participants experiencing an event during the specified observation period. Its breadth can be useful in an early-phase study focused on safety and tolerability, since it does not restrict counting to events judged to be caused by the study drug. At the same time, an event count alone does not convey event severity, duration, clinical importance, or whether investigators considered an event treatment-related. Those details require separate reporting.

The registry timeframe is up to 14 days after the last dose, up to approximately 42 days, excluding the pre-dose and screening period. The posted results include counts for active-treatment panels, pooled placebo, screening, and post-study. Screening and post-study counts should be kept distinct from treatment-period comparisons because they describe different periods and do not constitute randomized concurrent treatment arms. The endpoint is not the heart-rate measure described in the study hypothesis, and the adverse-event results cannot determine whether that hypothesis was satisfied.

7. Results Posted in the Registry

• Panel I - MK-8150 5/10/20/40 mg: 100.0% (12/12) versus 66.7% (24/36) on control; risk difference 33.3 percentage points (95% CI 17.9 to 48.7), risk ratio 1.50 (1.19–1.89); unadjusted two-proportion z-test p = 0.021.
• Panel J - MK-8150 10/20 mg: 83.3% (10/12) versus 66.7% (24/36) on control; risk difference 16.7 percentage points (95% CI -9.4 to 42.8), risk ratio 1.25 (0.89–1.76); unadjusted two-proportion z-test p = 0.271.
• Post Study: 1.0% (1/103) versus 66.7% (24/36) on control; risk difference -65.7 percentage points (95% CI -81.2 to -50.2), risk ratio 0.01 (0.00–0.10); unadjusted two-proportion z-test p = <0.001.
• Screening: 11.7% (12/103) versus 66.7% (24/36) on control; risk difference -55.0 percentage points (95% CI -71.6 to -38.4), risk ratio 0.17 (0.10–0.31); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event measure: each participant is counted according to whether an adverse event was recorded. The registry reports the number affected and the number at risk in each group. This presentation answers how many participants experienced at least one event under the stated definition; it does not count the total number of separate events or show how many events each participant experienced. The registry does not report a more detailed event-frequency analysis for this outcome.

How to read a risk difference

A risk difference compares the participant-level event proportions in two groups by subtracting one group’s proportion from the other. A value above zero indicates a larger observed proportion in the first group named in the comparison; a value below zero indicates a smaller observed proportion. Zero represents no difference in those proportions. The risk-difference estimates in the posted comparisons are unadjusted. They describe the observed groups and do not control for other factors or account for the study’s panel structure.

The Panel I comparison reports a positive risk difference of 0.333, with a confidence interval from 0.179 to 0.487. The Panel J comparison reports a risk difference of 0.167, with an interval from -0.094 to 0.428. The interval for Panel I excludes zero, whereas the interval for Panel J includes zero. That distinction describes the range of values compatible with each estimate under the interval method; it does not resolve concerns about small groups, multiplicity, or the applicability of a pooled comparator.

What the p-values describe

The unadjusted p-value is a measure of how compatible the observed data are with a specified no-difference null hypothesis, under the assumptions of the comparison method. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. The registry reports an unadjusted p-value of 0.021 for Panel I and 0.271 for Panel J. The record does not report a multiplicity adjustment, so these values should be read as unadjusted tests rather than as confirmatory evidence across the many outcomes and panels.

General statistical context: a confidence interval describes uncertainty around an estimate under the method’s assumptions. Wider intervals indicate less precision; narrower intervals indicate greater precision. In small groups, event counts can change substantially with the experience of only a few participants, so estimates and intervals should be interpreted cautiously. The reported intervals quantify sampling uncertainty for the stated comparisons, but they do not account automatically for design features, selection, missing observations, or multiplicity.

Planning illustrations are not observed power

The registry record includes planning illustrations based on the observed effect for the Panel J, post-study, and screening comparisons. These are not the trial’s original sample-size justification, and they are not observed power calculations. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set to the stated fraction of the observed effect. For the Panel J comparison, the illustration gives 105 participants per arm for 80% power and 140 participants per arm for 90% power at 100% of the observed effect; at 75%, it gives 198 and 264 participants per arm, and at 50%, 466 and 624 participants per arm, respectively. These are hypothetical planning values based on the observed comparison, not evidence that the study had a particular probability of detecting an effect.

General statistical context: sample-size planning depends on the effect size, event frequency, significance level, allocation, and analysis assumptions. Planning around a smaller effect generally requires a larger sample. Such illustrations should not be mistaken for the actual study design rationale, which is not reported in the registry record. The record also does not report the method used to construct the confidence intervals or test the comparisons, beyond identifying the reported comparisons as unadjusted.

10. Confidence Intervals and Precision

Precision is limited by the small number of participants in most treatment panels. The listed active-treatment group sizes range from 5 to 12 participants, while the pooled placebo group includes 36. With sparse group counts, an event in one additional participant can materially change the estimated group proportion. The posted confidence intervals for the two active-treatment comparisons illustrate uncertainty: the Panel I interval is 0.179 to 0.487, while the Panel J interval is -0.094 to 0.428. The first interval does not include zero; the second does.

A confidence interval should be read as a range of effect estimates compatible with the data under the statistical method and its assumptions, not as a guarantee that the true effect lies within the interval. It does not capture every source of uncertainty. In particular, these intervals do not address the implications of examining multiple outcomes and panels, and the registry does not report adjustment for multiplicity. They also do not make unlike panels directly comparable or remove concerns arising from the pooled placebo group and the crossover participants.

The risk-difference comparison for Panel I is more precise than the Panel J comparison in the sense that its reported interval is narrower, while both estimates are based on small numbers. The p-value and interval answer related but different questions: the interval conveys a range of plausible effect values, while the p-value describes compatibility with a specified null under the test assumptions. Neither should be interpreted without considering the design and the number of analyses.

The registry record does not report confidence intervals for each panel’s raw event count, nor does it report a precision analysis for the heart-rate hypothesis. Consequently, the uncertainty surrounding the principal scientific question in the brief summary cannot be assessed from these posted adverse-event results.

11. Multiplicity, Missing Data and Analysis Populations

The record lists 68 outcome measures and 105 analyses, while 28 secondary outcomes have posted results. It does not report a prespecified strategy for controlling the chance of false-positive findings across multiple outcomes, panels, time points, and dose regimens. The reported Panel I and Panel J p-values are explicitly unadjusted. They should therefore be interpreted as individual comparisons, not as multiplicity-controlled evidence across the full set of analyses.

The registry record does not report whether interim analyses were conducted, whether any analyses were prespecified beyond the outcome descriptions, or whether the posted comparisons were part of a formal hierarchy. It also does not report the statistical analysis plan, procedures for handling missing data, or imputation methods. No assumptions about those procedures can be made from the posted counts.

The primary outcome population is defined as all participants who received at least one dose of study drug. This is an exposed-participant population, not a stated intention-to-treat definition. The record does not report how many participants were randomized but did not receive treatment, whether any outcome data were missing, or how missing observations were handled. Thus, the displayed denominators describe the reported groups but do not, by themselves, establish that all randomized participants were included in every analysis.

The registry also pools placebo participants across Panels A through J and notes that the 8 Panel H crossover participants appear in both the Panel H MK-8150 and pooled placebo columns. This repeated representation should be considered when interpreting comparisons that treat the columns as separate groups. The record does not report a model accounting for within-participant correlation in that crossover panel or explain how the pooled comparator was handled statistically.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The serious adverse-event results report zero affected participants in each listed MK-8150 panel and in the pooled placebo group. The numbers at risk are 5 to 12 across active-treatment panels and 36 in the pooled placebo group. The serious-event terms list is empty. These results mean that the registry did not report a participant with a serious adverse event in those listed groups during the reported safety assessment; they do not show that serious events are impossible or that the underlying risk is zero.

The record’s deaths field is not populated with a count, so the number of deaths is not reported in the registry record. It should not be inferred from the serious adverse-event counts. The safety summary also includes screening and post-study groups, which are distinct from randomized treatment-period groups and should not be combined with them as if they were concurrent arms.

Zero serious events in small groups offers limited information about rare outcomes. The study’s group sizes and differing regimens constrain how precisely safety can be characterized. These figures also address serious adverse events, not all adverse events: the primary outcome reports non-serious and serious adverse-event participants together under its broad definition. Event severity, relatedness, and individual event details are not fully described in these counts. The findings are descriptive and should be read alongside the stated observation period and the specific panel structure.

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

The posted results establish that adverse events were recorded in participants across the active-treatment panels and in the pooled placebo group. The number of affected participants ranges from 3 among 5 in Panel D to 12 among 12 in Panel I; the pooled placebo count is 24 among 36. These counts are descriptive, and they show that the broad adverse-event outcome was not absent from either treatment assignment. The results do not identify which events were judged related to study drug or distinguish event severity in the primary outcome summary.

The unadjusted Panel I comparison has a positive risk difference and a reported interval excluding zero, whereas the Panel J comparison has an interval that includes zero. These are results from small groups and one set of unadjusted comparisons among many study outcomes and analyses. They do not establish that treatment caused the observed difference, and they do not determine whether the difference is clinically important. A p-value does not provide that judgment.

The reported absence of serious adverse events in the listed treatment and placebo groups is also limited by the small participant counts. It does not establish the absence of risk, and the registry record does not report a death count. Screening and post-study results are not direct randomized comparisons with treatment-period results.

Most importantly, the posted primary endpoint is not the heart-rate measure described in the study’s primary hypothesis. The record does not report the mean heart-rate contrasts, their uncertainty, or whether the stated threshold was met. The adverse-event counts therefore cannot answer the study’s heart-rate question. Nor do these counts establish the full safety, tolerability, pharmacokinetic, or pharmacodynamic profile of MK-8150. They are a limited report of participant-level adverse-event occurrence within the listed groups and observation period.

14. Why This Trial Matters Statistically

This study illustrates why early-phase trial results need to be read at the level of the design and endpoint, not only through the headline counts. Multiple panels cover distinct populations and dosing schedules, while the placebo result is pooled across panels. A single pooled comparator can be convenient for presentation, but it does not erase differences among the panel populations or regimens. The crossover participants are also represented in both the active-treatment and placebo columns, a detail that affects how apparent group separation should be understood.

The example also highlights the distinction between a broad safety endpoint and a focused physiologic hypothesis. The registry’s posted primary outcome counts participants with adverse events, while the brief summary’s main scientific hypothesis concerns a time-weighted average heart-rate increase and a specified threshold. Without the heart-rate results, the key hypothesis cannot be evaluated from the adverse-event data. Outcome labels and posted results therefore need to be checked against the question a reader wants answered.

Finally, the small panel sizes make uncertainty central to interpretation. Risk differences and confidence intervals convey more than counts alone, but unadjusted comparisons across multiple outcomes do not automatically support confirmatory conclusions. Planning illustrations based on observed effects can help describe hypothetical design requirements, yet they are not observed power and are not the original sample-size justification. Together, these features show why transparent reporting of analysis populations, missing-data methods, multiplicity plans, and endpoint-specific results matters for clinical research interpretation.

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 record does not report the results for the heart-rate hypothesis described in the study summary, even though that question is central to the stated scientific rationale. It also does not provide posted results for all listed outcome measures: 28 secondary outcomes have results, while the record lists 68 outcome measures. This limits any assessment of the full pharmacodynamic and safety evaluation.

Several treatment panels have small participant counts, and the panel regimens are not uniform. The treatment groups therefore do not form a simple dose-response sequence that can be interpreted from adverse-event counts alone. The placebo group is pooled across Panels A through J, and the record notes that Panel H crossover participants are represented in both the Panel H MK-8150 column and the pooled placebo column. The registry does not report a statistical model addressing this structure for the displayed comparisons.

The endpoint counts do not provide event-level detail about severity, duration, relatedness, or recurrence. The registry does not report missing-data procedures, an analysis plan, multiplicity control, interim analyses, or a sample-size justification. The listed planning illustrations are based on observed comparisons and do not substitute for the trial’s original design rationale. The death count is not reported in the registry record.

Finally, the screening and post-study comparisons are not randomized concurrent treatment comparisons. Their risk differences and p-values should not be interpreted as treatment effects. The registry does not provide enough detail to use those results as adjusted controls for the treatment-period findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150 (MK-8150-002) — NCT01656408.
• Registry record last updated 2018-09-25; status last verified 2018-08.
• Results first posted 2016-04-29.
• 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

NCT01656408 is a completed randomized, double-blind, phase 1 parallel-group multiple-dose study of MK-8150 and placebo. It enrolled 103 participants and included panels involving healthy participants and groups with hypertension, with varied dose and treatment schedules. The posted primary outcome counts participants with an adverse event among those who received at least one dose.

Adverse-event counts are reported for 10 MK-8150 panels and pooled placebo. The posted unadjusted comparisons include Panel I and Panel J against pooled placebo, as well as screening and post-study comparisons. Serious adverse events are reported for zero participants in the listed treatment and placebo groups; the number of deaths is not reported in the registry record.

The registry record does not report the heart-rate results needed to evaluate the stated heart-rate hypothesis. It also does not report a multiplicity strategy, missing-data methods, or the original sample-size justification. The available results are therefore a limited descriptive account rather than a complete report of the study’s planned safety and pharmacodynamic questions.