Safety, Tolerability and Pharmacokinetics Study of MK-7252 in Healthy Adult Participants (MK-7252-001): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and Pharmacokinetics Study of MK-7252 in Healthy Adult Participants (MK-7252-001) (NCT03326986), a randomized phase 1 study. The primary outcome is Number of Participants Who Experienced at Least One Adverse Event (AE).

2. Clinical Question

The wider study purpose was to assess safety, tolerability, pharmacokinetics and pharmacodynamics of MK-7252 in healthy adults. The registry describes ascending doses, and its summary says an amendment added a panel to examine higher doses and food effect after review of interim safety and preliminary pharmacokinetic data. The results include the primary adverse-event endpoint and posted pharmacokinetic outcomes, but the available comparison highlighted is specifically the 72 mg dose versus placebo.

The question is therefore narrow: what adverse-event counts were recorded at that dose, and how uncertain is the estimated difference from placebo? The results can describe what was observed in the posted groups. They do not establish whether an event was caused by treatment, and they do not answer whether MK-7252 is effective for a disease.

3. Trial Design

The registry identifies this as a Phase 1, randomized, quadruple-masked, parallel study of MK-7252 and placebo. It lists planned enrollment of 24 and a completed status. The recorded study dates are 2017-11-10 for study start and 2018-12-17 for primary completion. The study description concerns healthy adults.

The treatment description includes multiple dose levels and repeated treatment periods. Participants in Panels A and B were described as receiving a single dose of MK-7252 or placebo in each of five alternating treatment periods, in a fasted state. Panel C was described as receiving treatment in up to five dosing periods and included a food-effect assessment. The summary states that treatment periods were separated by a 7-day washout period. These details describe the registry entry; further operational details are not reported in the registry record.

The posted safety results are organized by dose rather than simply by a single treatment arm. The registry says adverse events are reported by the dose taken at the time of the event, not by panel or period, and that placebo adverse events are pooled across periods and panels. Consequently, the dose-specific counts shown in the results are not a straightforward account of participants assigned to only one dose throughout the study. The registry lists 12 participants in the 72 mg group and 22 in the pooled placebo group for the primary comparison.

There are 17 outcome measures in the record, including adverse events and pharmacokinetic outcomes. The record posts 15 secondary outcomes. It does not report a full statistical analysis plan or explain the original rationale for the design and enrollment.

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: Participants in Panels A and B received a single-rising dose of MK-7252 or placebo in 5 alternating dosing periods. Participants in Panel C received a single-rising dose of MK-7252 or placebo in 3/5 planned periods (P). A 180 mg dose was added (P3). P4-5 were not run so the 240, 360, 540, and 120 mg fed and placebo fed doses were not given.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of study treatment and experienced an AE during the study period

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: All randomized participants

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced at Least One Adverse Event (AE), measured over Up to approximately 21 weeks.

The primary endpoint is the number of participants who experienced at least one adverse event, assessed up to approximately 21 weeks. An adverse event is defined as an untoward medical occurrence in a participant who received study treatment; the event need not have a causal relationship with treatment. Worsening of a pre-existing condition that is temporally associated with study treatment also meets the registry definition.

This endpoint is used to summarize how many participants had one or more such occurrences. It is a participant count, not a count of every event: a participant with multiple events is still counted once for this endpoint. The definition is broad and does not by itself attribute an event to MK-7252 or indicate its severity. Serious adverse events are reported separately in the safety results.

The registry defines the primary analysis population as all participants who received at least 1 dose of study treatment and experienced an adverse event during the study period. In the posted comparison, 7 of 12 participants in the MK-7252 72 mg group and 15 of 22 in the pooled placebo group experienced at least one adverse event. Those counts provide a descriptive comparison, but they do not describe event types or establish why the events occurred.

7. Results Posted in the Registry

• MK-7252 72 mg: 58.3% (7/12) versus 68.2% (15/22) on control; risk difference -9.8 percentage points (95% CI -43.9 to 24.2), risk ratio 0.86 (0.49–1.49); unadjusted two-proportion z-test p = 0.566.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted comparison expresses the primary endpoint as a difference in the proportions of participants with at least one adverse event. The registry reports 15 of 22 participants in the pooled placebo group and 7 of 12 in the MK-7252 72 mg group. It gives a risk difference of -0.099. A risk difference is an absolute contrast between the two group proportions; a negative estimate reflects a lower observed proportion in the 72 mg group than in placebo. The estimate is based on the posted summaries, and it should be interpreted together with its confidence interval.

What does a confidence interval describe?

In general, a confidence interval gives a range of estimates compatible with the data under the statistical procedure used. It communicates precision: a wider interval indicates that the data permit a broader range of possible values. It is not a guarantee that the true value lies in the displayed range, nor is it a range of individual participant outcomes. The interval for this risk difference runs from -0.439 to 0.242 and includes zero. The registry does not identify the interval calculation method.

How should the p-value be read?

The posted unadjusted p-value is 0.566. In general, a p-value describes how unusual data at least as inconsistent with a specified no-difference model would be, if that model and the analysis assumptions were correct. It is not the probability that there is no difference, and it does not measure the size or clinical importance of a contrast. The registry does not report the full testing procedure or statistical analysis plan for this result, so the p-value should be read as the unadjusted value displayed for this comparison.

What are the relative measures?

The record also gives a risk ratio and an odds ratio with intervals. A risk ratio compares the two group proportions as a ratio; an odds ratio compares the odds of an event. These are relative measures, whereas the risk difference is an absolute measure. The risk-ratio interval is 0.490 to 1.493, and the odds-ratio interval is 0.152 to 2.804. Both ranges include their no-difference reference value. The registry does not report the methods used to construct these intervals.

What does the endpoint count?

This is a binary participant-level endpoint: each participant is classified according to whether they experienced at least one adverse event. It does not count repeated events separately. The registry defines an adverse event broadly, without requiring a causal relationship to study treatment. It also states that event results are attributed to the dose taken at the time of the event, with placebo results pooled across panels and periods. This reporting arrangement matters when comparing the listed dose-specific counts.

What analysis details are unavailable?

The registry record does not report the full statistical plan, the method used for the primary comparison, prespecified adjustment for multiple comparisons, interim-analysis methods, or a missing-data approach. It also does not report the original sample-size justification. Those omissions prevent a complete assessment of whether the displayed comparison follows a prespecified plan or how analysis choices were made. The posted summary statistics permit a descriptive reading, but not a reconstruction of every analytic decision.

General statistical interpretation also depends on the study’s sampling and allocation structure. Here, the study is identified as randomized and parallel, while the treatment descriptions involve multiple dosing periods and the posted safety data are dose-specific. The record explains the pooling convention for placebo, but does not provide enough detail to infer additional design or analysis features beyond those descriptions.

10. Confidence Intervals and Precision

The main precision result is the confidence interval around the risk difference for MK-7252 72 mg versus placebo. The point estimate is -0.099, and the interval extends from -0.439 to 0.242. Because it includes zero, it does not distinguish the observed data from a range that includes no absolute difference. Its extension in both directions also shows that the posted data do not pin down the direction or magnitude precisely.

In general, confidence intervals are useful because a point estimate alone can give a false sense of certainty. The interval represents uncertainty in the estimated group contrast, not the range of event rates that every future study must observe. The registry does not state the method used to calculate this interval, so its exact construction cannot be assessed from the record.

The relative intervals are also broad: 0.490 to 1.493 for the risk ratio and 0.152 to 2.804 for the odds ratio. Both include the value corresponding to no relative difference. The three effect measures express the comparison on different scales; none removes the uncertainty arising from the available data.

The denominators in the 72 mg and placebo comparison are 12 and 22. This is a small comparison, and the interval is consistent with a wide range of possible effects. The placebo count is pooled across periods and panels, as described in the registry. That feature should be kept in view when considering the precision and interpretation of the contrast. The record does not report a precision target or a clinically important threshold for this endpoint.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size table and curve are planning illustrations based on the observed effect in the posted 72 mg versus placebo comparison. The figures are participants per arm, not total events. This comparison is a binary participant outcome, so the table gives participants per arm. The general note for time-to-event outcomes in the registry says those tables would give total events, but that is not the case.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. These assumptions describe the illustration; the original trial’s sample-size assumptions are not reported in the registry record.

The table gives participants per arm for 80% power and participants per arm for 90% power. In plain terms, these columns show the planned number in each of two equally sized groups under the stated assumptions to have the specified chance of detecting the assumed effect if that effect were present. They are planning quantities, not counts from the study. This is not observed power.

For 100% of the observed effect, the illustration gives 375 participants per arm for 80% power and 502 for 90% power. For 75% of the observed effect, it gives 658 and 881 participants per arm, respectively. For 50% of the observed effect, it gives 1,458 and 1,951 participants per arm, respectively. The table illustrates that smaller effects require more participants under the stated assumptions. These figures depend on treating the observed effect as the starting point, so they should not be read as a recommended design or as evidence about the original design.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.682; treatment proportion p₁ = 0.583; average p̄ = 0.633.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6818 = 1.3363.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6782 = 0.5708.
4. n = (1.3363 + 0.5708)² / (-0.0985)² = 375.0, rounded up to 375 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.681818181818182                          # control proportion
p1 <- 0.583333333333333                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(3326986)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 375 (80% power), 502 (90% power)
 75% of observed effect: n per arm = 658 (80% power), 881 (90% power)
 50% of observed effect: n per arm = 1,458 (80% power), 1,951 (90% power)
power.prop.test: 375 
Simulated power at n = 375 per arm: 0.802 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The record includes 17 outcome measures and reports 15 secondary outcomes. It lists several pharmacokinetic measures, including area-under-the-curve measures, maximum concentration, concentrations at specified postdose times, and time to maximum concentration. A number of outcomes and dose groups create opportunities for multiple comparisons, but the registry record does not report a multiplicity-adjustment plan for the posted results.

The 72 mg adverse-event comparison has an unadjusted p-value of 0.566. Because it is explicitly unadjusted, it should not be treated as if it accounts for testing across all doses or outcomes. The record does not report which comparisons were prespecified, whether a hierarchy or other testing strategy was used, or whether the displayed result was selected from a larger set of analyses. This limits how strongly the p-value can be interpreted as confirmatory evidence.

The registry provides the primary endpoint population as participants who received at least 1 dose of study treatment and experienced an adverse event during the study period. It does not give a full account of analysis populations or explain how participants without an event were represented in each analysis denominator beyond the posted group summaries. The missing-data approach, handling of withdrawals, and treatment of incomplete follow-up are not reported in the registry record.

It is also not reported whether there were interim analyses or how any interim information affected formal inference. The summary mentions review of interim safety and preliminary pharmacokinetic data before an amendment added Panel C, but it does not describe statistical monitoring boundaries or a testing adjustment. No such details should be inferred from the mention of a review.

These gaps do not invalidate the descriptive counts. They do mean that readers cannot fully assess the prespecification, multiplicity control, or missing-data handling behind the posted inferential result. The endpoint comparison and its uncertainty are best read as the registry presents them, alongside these unreported analysis details.

14. 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 results list zero participants with a serious adverse event in every dose group, in placebo, and in the post-study group. The record also lists zero deaths. These are observed counts in the reported groups; they do not establish that serious events could not occur or characterize the frequency of rare outcomes beyond this study.

For other adverse events, the registry reports participants with at least one event rather than a count of all events. For example, the primary endpoint comparison lists 7 of 12 in the MK-7252 72 mg group and 15 of 22 in placebo. The registry says these events are reported by dose taken at the time of the event, and placebo events are pooled across periods and panels. The dose-specific groups therefore should be read in light of that reporting convention.

The adverse-event definition includes occurrences that do not necessarily have a causal relationship to study treatment. Counts describe what was recorded, not what caused it. Event types and a complete clinical characterization are not presented in the primary endpoint count.

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

The posted data show how many participants were recorded as having at least one adverse event at each listed dose and in pooled placebo. For the highlighted 72 mg comparison, the observed counts were 7 of 12 and 15 of 22, respectively. The risk-difference estimate is -0.099, with a confidence interval from -0.439 to 0.242. This is a descriptive contrast with substantial uncertainty, not a precise estimate of a treatment effect.

The confidence interval includes zero, and the unadjusted p-value is 0.566. These results do not establish a clear difference between the groups, but absence of a clear difference is not proof that the groups are equivalent. The registry does not report an equivalence margin or a non-inferiority objective. The small group denominators also limit how much can be inferred from the observed counts.

The endpoint is broad: it records any qualifying adverse event without requiring that it be caused by the study treatment. The count does not convey the full nature, duration, or importance of each event. Separate serious-event results list no serious adverse events and no deaths in the reported groups. Those observations apply to this study record and do not establish what would occur in a larger or different population.

The study was conducted in healthy adults and its stated purpose was to assess safety, tolerability, pharmacokinetics and pharmacodynamics. The results do not answer whether MK-7252 benefits people with cancer or another condition. Nor do the posted data establish that all dose levels have the same safety profile. Dose groups, periods, and the pooled placebo results have specific reporting structures, and the record does not report a formal dose-response analysis.

Overall, the result is most appropriately read as an early-phase description of recorded adverse events with a wide range of plausible group contrasts. The registry does not provide the full statistical plan, so conclusions about prespecification and multiplicity cannot be made from the posted summary alone.

16. Why This Trial Matters Statistically

This study illustrates why a numerical comparison should be read together with its endpoint definition, group structure, and uncertainty. The primary outcome is not a count of all adverse events; it is a count of participants with at least one event. That distinction affects what the results can describe. The broad event definition also means that a recorded event is not necessarily attributed to treatment.

The dose-specific safety counts need context. The record describes multiple dosing periods, reports events by the dose taken when they occurred, and pools placebo events across periods and panels. That arrangement is important when interpreting the 72 mg versus placebo estimate. The apparent simplicity of a two-group contrast does not capture the full treatment-period structure described in the study entry.

The confidence interval and unadjusted p-value also demonstrate that an estimate can be directionally lower in one group without providing a precise or definitive comparison. The interval includes zero and spans values on either side of it. In a study with small reported dose-specific groups, the interval is central to interpretation; the point estimate alone is not enough.

Finally, the record lists multiple outcomes and dose groups but does not report a full statistical analysis plan or multiplicity strategy. This makes it important to distinguish descriptive results from results that can be interpreted as confirmatory. The sample-size illustration offers a planning perspective based on the observed effect, but it is not evidence of the trial’s original design rationale. Together, these features make the study a useful example of interpreting early-phase safety data cautiously and transparently.

17. 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 principal limitation for interpreting the highlighted comparison is the small number of participants in each reported group: 12 for MK-7252 72 mg and 22 for pooled placebo. The confidence interval is correspondingly broad and includes values on either side of no difference. The registry does not report a target precision or a clinically meaningful threshold for the endpoint.

The study description involves treatment across multiple periods, while adverse events are summarized by dose at the time of the event and placebo events are pooled across periods and panels. The record does not provide enough detail to assess how this structure affects every comparison or whether period-related effects were addressed analytically.

The primary endpoint is a broad count of participants with any qualifying adverse event. It does not identify causality, and the primary count does not convey the types or severity of non-serious events. Although serious adverse events and deaths are listed separately, the record does not provide a detailed account of event timing or clinical course in the information.

The full statistical analysis plan, original sample-size justification, multiplicity approach, missing-data handling, interim-analysis methods, and complete analysis-population definitions are not reported in the registry record. These omissions restrict assessment of prespecification and robustness. The registry also lists 17 outcome measures while posting 15 secondary outcomes, so not every listed outcome has a posted result in the record.

The participants were healthy adults, and the study’s stated purpose was early-phase safety, tolerability, pharmacokinetics and pharmacodynamics. The results therefore have limited scope for interpreting outcomes in other populations or for answering questions about treatment benefit.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Safety, Tolerability and Pharmacokinetics Study of MK-7252 in Healthy Adult Participants (MK-7252-001) — NCT03326986.
• Registry record last updated 2020-01-09; status last verified 2019-12.
• Results first posted 2020-01-09.
• 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.

21. Record Summary

This completed Phase 1 study, NCT03326986, examined MK-7252 safety, tolerability, pharmacokinetics and pharmacodynamics in healthy adults. The registry lists randomized allocation, quadruple masking, a parallel model and planned enrollment of 24. The recorded start date is 2017-11-10, and primary completion is listed as 2018-12-17.

The primary endpoint counted participants with at least one adverse event up to approximately 21 weeks. In the posted 72 mg versus placebo comparison, the counts were 7 of 12 and 15 of 22. The risk difference was -0.099, with a confidence interval from -0.439 to 0.242 and an unadjusted p-value of 0.566. The interval shows substantial uncertainty around the contrast.

The registry lists zero serious adverse events and zero deaths across the reported dose, placebo and post-study groups. Multiple pharmacokinetic outcomes are listed, but the full statistical plan and several analysis details are not reported in the registry record.