Evaluation of MK-1075 in Participants With Hepatitis C Virus (HCV) Infection (MK-1075-002): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of MK-1075 in Participants With Hepatitis C Virus (HCV) Infection (MK-1075-002) (NCT02392494), a non-randomized phase 1 study. The primary outcome is Percentage of Participants Experiencing an Adverse Event (AE).

2. Clinical Question

3. Trial Design

This was a Phase 1 study of MK-1075 in HCV-infected participants, with a sequential, non-randomized design and no masking. The registry record gives the study title as a single rising dose study. It lists enrollment of 9 and four dose panels: a single 100 mg dose in Panel A, a single 200 mg dose in Panel B, a single 400 mg dose in Panel C, and a single 800 mg dose in Panel D. The sponsor is Merck Sharp & Dohme LLC.

The study started on 2015-04-28, had a primary completion date of 2015-08-10, and is recorded as completed. The stated purpose was to evaluate safety and pharmacokinetics and determine the ability of MK-1075 to reduce HCV viral load following a single dose. The primary endpoint described in the registry record is the percentage of participants experiencing an adverse event up to Study Day 14.

Because allocation was non-randomized and the model was sequential, dose panels are not randomized groups intended for a like-for-like causal comparison. Differences between panel results, if reported, could reflect factors other than dose; the record does not describe a comparative design that would separate those influences. The specific sequence and operational rules used to move between doses are not reported in the registry record. Details of eligibility criteria, masking procedures beyond the listed absence of masking, and the planned statistical analysis are also not reported in the registry record.

The safety counts list participants at risk in the 100 mg, 200 mg, and 400 mg panels. Numerical safety counts for the 800 mg panel are not reported in the registry record. The record lists 3 outcome measures and no analyses. It does not report results for pharmacokinetics or viral load in the information.

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: Nine participants were enrolled and allocated to single doses of either 100, 200, or 400 mg of MK-1075. As per the protocol, planned Panel D (800 mg MK-1075) was not enrolled since the study objective was achieved in Panel C.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All Participants as Treated (APaT): all participants who received at least 1 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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Experiencing an Adverse Event (AE), measured over Up to Study Day 14.

The primary endpoint is the percentage of participants experiencing an adverse event up to Study Day 14. The registry defines an adverse event broadly as an untoward medical occurrence after administration of a pharmaceutical product; the event does not have to be causally related to the treatment. The definition includes an unfavourable or unintended sign, symptom, disease, or abnormal laboratory finding temporally associated with a medicinal product or protocol-specified procedure. Worsening of a pre-existing condition can also qualify when temporally associated with the sponsor’s product.

This endpoint is used to describe short-term safety and tolerability observations after a single dose. Counting all qualifying events without requiring a causal attribution helps capture occurrences that merit recording, while not establishing that the study drug caused them. The outcome is reported as a percentage for each treatment panel, and the population is All Participants as Treated: participants who received at least one dose of study drug.

The registry record describes the measure but does not report the endpoint percentages. It does list counts of participants with serious and other adverse events for some dose panels. Those counts should not be mistaken for the complete set of endpoint percentages or for a causal assessment. The specified observation window also limits the endpoint to events recorded up to Study Day 14; it does not describe longer-term safety.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation starts with identifying the endpoint, population, and observation period. The endpoint is a percentage of participants with an adverse event, the population is All Participants as Treated, and the timeframe is up to Study Day 14. This is a binary participant-level outcome: each participant either experienced at least one qualifying event during the defined period or did not. The measure is not a count of every event, because the endpoint is the percentage of participants experiencing an event.

In general, a percentage for a binary outcome is based on the number of participants with the outcome relative to the number evaluated. The registry record describes the endpoint in percentage terms, but the endpoint percentages are not reported in the record. The safety entries instead give numbers at risk and numbers affected for serious and other adverse events in the listed dose panels. No new percentages can be inferred without turning those counts into calculations, so the interpretation should retain the counts as posted.

What can a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimated quantity. It helps readers distinguish a precise estimate from one that could plausibly vary widely because the data are limited. For a binary outcome, the observed proportion is subject to sampling variability: another group of participants from a similar population might have a different observed frequency. Small participant counts generally make that uncertainty especially important. The registry record does not report confidence intervals for the primary endpoint.

A confidence interval would not, by itself, show that MK-1075 caused an event or that one dose is safer than another. It quantifies uncertainty under the assumptions of the method used to construct it. In a non-randomized study without a listed control group, even a precisely estimated frequency would remain a descriptive frequency among participants studied, not a controlled estimate of a treatment effect.

Why does the design matter?

Random allocation, when used, is intended to make comparison groups similar on average with respect to measured and unmeasured characteristics. This study is listed as non-randomized and sequential, with no masking. The dose panels therefore should not be interpreted as if assignment had created exchangeable groups. A difference in event counts across panels could reflect differences in participants, timing, or other factors, as well as any dose-related influence. The registry record does not report a statistical method for adjusting for such factors or a planned inferential comparison.

Sequential design describes the study model, but it does not establish the exact procedures used to assign participants to dose panels. The specific order, decision rules, and any dose-escalation criteria are not reported in the registry record. Those details should not be inferred from the study title alone.

What do the planning illustrations represent?

In general, sample-size planning illustrations ask how many participants might be needed to detect a chosen effect under specified assumptions. They are not observed study results and do not describe the number of participants actually enrolled. The planning approach described for this analysis uses the observed effect as a reference, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial used that design or conducted that analysis.

The study itself is non-randomized and sequential, whereas the planning illustration assumes equal allocation between two arms. A hypothetical calculation based on those assumptions is therefore not a reconstruction of the study’s own design. It also is not observed power. The registry record does not report a sample-size justification or its own planned power calculation. Any planning estimate should be interpreted as conditional on its assumptions, not as a statement about the probability that the trial detected an effect.

Finally, the registry record lists no analyses. It does not provide an inferential model, adjustment strategy, missing-data procedure, or multiplicity procedure. Statistical concepts can explain what such methods would generally address, but they cannot fill in the details of an unreported plan. The most defensible interpretation is consequently descriptive: retain the listed event counts, recognize the short follow-up and small groups, and avoid causal or between-dose conclusions not supported by the record.

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("MK-1075 100 mg (Panel A)", "MK-1075 200 mg (Panel B)", "MK-1075 400 mg (Panel C)")
n      <- c(3, 3, 3)
events <- c(2, 2, 1)
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  MK-1075 100 mg (Panel A)  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2
ARM  MK-1075 200 mg (Panel B)  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2
ARM  MK-1075 400 mg (Panel C)  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 3 outcome measures, but the information identifies the adverse-event endpoint and does not provide complete results for the other outcomes. It lists no analyses. A multiplicity procedure—such as a plan for controlling the chance of false-positive findings when several outcomes or comparisons are assessed—is not reported in the registry record. The record also does not report whether formal hypothesis tests were planned. Without that information, no claim about multiplicity control can be made.

The primary endpoint population is All Participants as Treated: all participants who received at least one dose of study drug. This is a treatment-exposure population definition, not a description of how missing observations were handled. The registry record does not report the amount of missing endpoint data, reasons for any missingness, or an imputation or sensitivity-analysis method. It also does not report whether all participants contributed endpoint information through Study Day 14.

In general, missing-data methods matter because results can be affected when outcome information is unavailable, especially if missingness is related to participant experience or treatment exposure. The record does not give enough information to assess whether missingness occurred or how it might influence the reported counts. Analysis populations for outcomes other than the primary endpoint are not reported in the registry record. No assumptions about analysis sets, exclusions, multiplicity adjustments, interim analyses, or missing-data handling should be inferred.

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 counts are 0 among 3 participants at risk in the 100 mg panel, 0 among 3 in the 200 mg panel, and 0 among 3 in the 400 mg panel. The record lists 0 deaths in each of those panels. For other adverse events, the counts affected are 2 among 3 at risk in the 100 mg panel, 2 among 3 in the 200 mg panel, and 1 among 3 in the 400 mg panel. These are counts, not percentages, and no percentage conversion is made.

No serious adverse event terms are listed. The record does not report corresponding safety counts for the 800 mg panel. A zero count in a small observed group means that no event of that category was recorded in that group during the reported observation; it does not demonstrate that the event cannot occur. The listed counts are descriptive and do not establish that MK-1075 caused or prevented an event. The registry record does not report a randomized control group or a statistical comparison that would support a comparative safety conclusion.

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

The registry record establishes that MK-1075 was studied as a single dose in HCV-infected participants, with safety, pharmacokinetics, and viral-load reduction among the stated aims. It identifies a short-term adverse-event endpoint and provides counts for serious and other adverse events in the 100 mg, 200 mg, and 400 mg panels. These observations describe what was recorded among participants at risk in those panels.

The counts do not establish causality. The adverse-event definition explicitly does not require a causal relationship to study drug, and the record does not present a causal analysis. The non-randomized, sequential design and lack of a listed control group also mean that the dose panels are not controlled comparisons. The counts should not be interpreted as demonstrating that one dose has a greater or smaller risk than another.

The record does not provide the primary endpoint percentages, confidence intervals, hypothesis tests, or results for the 800 mg panel. It also does not report pharmacokinetic or viral-load findings in the information. Therefore, the safety counts cannot answer whether the study met its other aims, and they do not quantify the precision of the adverse-event frequency.

In general, an early-phase study can describe initial observations under its specific conditions, while leaving substantial uncertainty about event frequencies and comparisons. Here, the small numbers at risk and the limited observation period mean the counts are narrow in scope. They do not establish longer-term safety, generalizability to other populations, or a treatment benefit. The record supports a descriptive reading of the posted events, not a broader clinical conclusion.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a dose-escalation-style question and a controlled comparison. Its sequential, non-randomized model allows the record to describe observations across single-dose panels, but does not provide the design basis for treating the panels as equivalent groups. That distinction is central when interpreting event counts: a numerical difference between groups is not automatically evidence of a dose effect.

The primary outcome is participant-level and binary, and its stated window is up to Study Day 14. The listed counts convey the number of affected participants, but the endpoint is defined as a percentage and those endpoint percentages are not reported in the registry record. This highlights why the form of a registered outcome and the form of the posted results both matter. Readers need the estimate and its uncertainty to understand how much information the observed data contain.

The record also illustrates the limits of sparse safety observations. It reports no serious adverse events among the listed participants at risk, while other adverse events are recorded in the listed panels. In general, a small observed sample can provide an initial descriptive signal but cannot precisely characterize uncommon outcomes. Without interval estimates or a control group, the counts cannot establish comparative risk.

Finally, the trial’s stated aims extend beyond the safety endpoint to pharmacokinetics and viral-load change, but those results are not reported in the registry record. Keeping each question distinct prevents safety observations from being used to answer efficacy or pharmacokinetic questions. The statistical value of this record is therefore in clarifying the study’s design, endpoint, and limits of 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.

Several limitations are specific to the information reported for this study. First, the study is non-randomized and sequential, and no control group is listed. Dose-panel counts are consequently descriptive rather than like-for-like comparative estimates. The registry record does not report the exact sequence of dose administration, escalation criteria, or any rules that governed progression between panels.

Second, enrollment was 9, and the safety counts list 3 participants at risk in each of the 100 mg, 200 mg, and 400 mg panels. The record does not report safety counts for the 800 mg panel. The small listed groups limit how much can be learned about event frequency, particularly for less common events. The short endpoint timeframe, up to Study Day 14, also does not describe longer-term outcomes.

Third, the registry record describes the primary endpoint as a percentage but does not report those percentages or confidence intervals. No statistical analyses are listed. It does not report results for the stated pharmacokinetic and viral-load aims in the information. Participant characteristics, detailed eligibility criteria, missing-data handling, analysis procedures, multiplicity plans, and any interim analyses are not reported in the registry record.

These omissions limit assessment of precision, completeness, and the basis for any comparisons. They do not establish that a procedure or analysis was absent from the study; they mean that it is not reported in the registry record. Interpretation should remain restricted to the design details and descriptive safety counts that are recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of MK-1075 in Participants With Hepatitis C Virus (HCV) Infection (MK-1075-002) — NCT02392494.
• Registry record last updated 2019-01-22; status last verified 2019-01.
• Results first posted 2018-12-31.
• 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

NCT02392494 is a completed Phase 1 study of single-dose MK-1075 in participants with hepatitis C virus infection. It is listed as sequential, non-randomized, and unmasked, with enrollment of 9. The dose panels are 100 mg, 200 mg, 400 mg, and 800 mg. The primary endpoint is the percentage of participants experiencing an adverse event up to Study Day 14, in the All Participants as Treated population.

Safety counts are reported for the 100 mg, 200 mg, and 400 mg panels: each lists 3 participants at risk, with 0 serious adverse events and other adverse events affecting 2, 2, and 1 participants, respectively. The record lists 0 deaths in each of these panels. It does not report endpoint percentages, safety counts for the 800 mg panel, or statistical analyses. Although pharmacokinetics and viral-load reduction are stated study aims, results for those aims are not reported in the registry record.