MK-1006 Single Dose Study in Japanese Type 2 Diabetes Patients (MK-1006-005): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MK-1006 Single Dose Study in Japanese Type 2 Diabetes Patients (MK-1006-005) (NCT00791661), a randomized phase 1 study. The primary outcome is Number of Participants Who Experienced at Least One Adverse Event.

2. Clinical Question

This was a safety-focused, single-dose study rather than a trial designed to establish a clinical benefit. The registry also lists pharmacokinetic and pharmacodynamic outcomes, including plasma concentration measures and 24-hour weighted mean glucose concentration. Their results are not reported in the registry record in the registry record for this analysis.

3. Trial Design

The study, MK-1006-005, is recorded as a randomized, double-masked, parallel Phase 1 trial. Its status is completed. The registry gives a start of 2008-11 and primary completion of 2009-03. The sponsor is Merck Sharp & Dohme LLC.

The study description calls this a single rising dose study in Japanese participants with type 2 diabetes. Three panels are described. Panel A includes MK-1006 doses of 15 mg, 30 mg, and 45 mg; Panel B includes 60 mg, 80 mg, and 60 mg in the fed state; Panel C includes 100 mg, 140 mg, and 170 mg. Each description states that there was a 7-day wash-out period between doses and that participants could have received both MK-1006 and matching placebo over the three treatment periods.

The record labels the overall model as parallel while also describing treatment periods in which participants could receive active drug and placebo. How that period structure relates to the randomized parallel model is not reported in the registry record. The posted group counts therefore describe the outcome records for each treatment group, not necessarily separate groups of people. The primary outcome population explicitly allows the same participant to appear in more than one arm.

Enrollment is listed as 24. The primary endpoint counts are reported separately for each dose and placebo group, with group sizes ranging from 2.0 to 15.0. The reported groups are not equal in size. No further detail on sequence assignment, allocation concealment, or the rationale for the group sizes is reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Period 1

7 Day Wash-out

Reasons for not completing this period:

Period 2

7 Day Wash-out

Analysis population for the primary outcome, as defined in the registry: Participants who received study drug. The same participant may appear in more than one treatment arm.

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 Number of Participants Who Experienced at Least One Adverse Event, measured over from the time of the run-in period prior to the first dose of study drug through the end of the poststudy period (up to approximately 31 days).

The primary endpoint counts participants who experienced at least one adverse event. An adverse event is defined in the registry as an unfavorable and unintended change in the body's structure, function, or chemistry temporally associated with study drug use, whether or not it was considered related to the product. The timeframe runs from the run-in period before the first dose through the end of the poststudy period, up to approximately 31 days.

This endpoint is used to describe the frequency of participants with any recorded adverse event during the stated observation period. Counting participants with at least one event gives a participant-level summary: repeated events in the same participant do not increase that participant's endpoint count. The measure does not distinguish event severity, seriousness, or attribution to study drug. Those distinctions require separate safety information.

The endpoint is a count, not a measure of event rate over person-time. It also does not by itself compare risk statistically between groups. The registry presents counts and group sizes, but a formal treatment comparison and its uncertainty are not reported in the registry record. The results should therefore be read as descriptive safety counts for the posted groups, rather than as a tested difference between MK-1006 and placebo.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either had at least one adverse event during the specified period or did not. The registry reports the number of participants with an event and the size of each treatment group. Such counts are straightforward to describe, but statistical comparison requires careful attention to denominators, dependence between observations, and the analysis population.

What does a confidence interval add?

General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity, such as an event proportion or a contrast between groups. It helps distinguish a precise estimate from one that remains compatible with a wide range of values. The registry record does not report confidence intervals for the primary endpoint. No interval can be quoted for these results without calculating a new estimate, which would not be the sponsor's posted analysis.

Why do the group sizes and repeated participation matter?

The group sizes differ, from 2.0 in the placebo-fed group to 15.0 in the placebo group. General statistical explanation: when denominators differ, raw counts alone do not compare event proportions fairly. The registry also states that the same participant may appear in more than one treatment arm. This means observations across groups may not be independent; treating every arm entry as a different person could understate uncertainty. The record's parallel-model label and its descriptions of participants receiving treatments across periods leave the exact relationship between treatment assignments and repeated group entries unclear.

What would a formal comparison require?

General statistical explanation: a treatment comparison would ordinarily define the contrast of interest, the population being compared, and the statistical method used to account for the design. For repeated observations from the same participant, an analysis may need to account for within-participant dependence. The registry record does not report a primary statistical test, adjustment method, model, or confidence interval for the event-count comparison. The posted counts should therefore be read descriptively, not as an inferential finding.

The registry lists an assumption set for planning illustrations: a two-sided significance level of 0.05, equal allocation, a normal approximation, and a target effect expressed as a fraction of the observed effect. It states that these are planning illustrations calculated from the observed effect, not the trial's own design. No planning values are included in the registry record for this record, and such illustrations would not be observed power or a description of the trial's original sample-size justification. That justification is not reported in the registry record.

The registry identifies the primary measure as a number of participants with an event. A count of affected participants is not the same as an event total: multiple events in one participant do not necessarily create multiple affected participants for this endpoint. It is also not a time-to-event measure. The posted outcome does not provide event timing, recurrent-event counts, exposure-adjusted rates, or participant-level data.

General statistical explanation: over-dispersion is relevant when count data vary more than a simple statistical model expects. It is not the central issue for this primary endpoint as described, because the reported value is the number of people with at least one event rather than the total number of events. Event-level counts or recurrent events might raise different modeling questions, but those data and analyses are not reported in the registry record.

The record reports 13 analyses and lists 8 outcome measures, as well as 6 posted secondary outcomes. These counts alone do not specify which analysis corresponds to each outcome or how the analyses were organized. The registry does not report whether analyses were prespecified, whether any interim analyses took place, or how multiple comparisons were handled. No assumptions about those features can be made from the outcome listings alone.

The secondary outcomes have different statistical forms. Plasma concentration summaries such as Cmax and AUC describe pharmacokinetic measurements; Tmax is a median time measure, apparent terminal half-life describes drug disposition, and weighted mean glucose is a pharmacodynamic measure. General statistical explanation: the appropriate summary and uncertainty measure depend on the distribution and design of each outcome. The values and methods for these secondary analyses are not reported in the registry record, so their numerical behavior cannot be evaluated.

For the posted primary counts, the clearest statistical reading is to retain the reported numerator and group size together, note that the groups are unequal, and avoid interpreting the count pattern as a proven dose trend or treatment contrast. The record does not report a dose-response model or a prespecified comparison between any dose and placebo. The outcome data also do not provide an estimate of the magnitude or precision of a causal effect.

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-1006 15 mg", "MK-1006 30 mg", "MK-1006 45 mg", "MK-1006 60 mg", "MK-1006 60 mg Fed", "MK-1006 80 mg")
n      <- c(6, 6, 6, 6, 6, 6)
events <- c(1, 1, 0, 1, 1, 3)
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-1006 15 mg  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  MK-1006 30 mg  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  MK-1006 45 mg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  MK-1006 60 mg  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  MK-1006 60 mg Fed  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  MK-1006 80 mg  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy for the primary and secondary outcomes or for the multiple dose groups. The listed secondary outcomes include several pharmacokinetic measures and a glucose measure, and the record reports 13 analyses. These listings do not establish which results were treated as confirmatory, whether any adjustment for multiple comparisons was used, or how hypotheses were ordered. Those details are not reported in the registry record.

Missing-data handling is also not reported in the registry record. The posted group sizes give the numbers associated with the outcome results, but the record does not describe missing observations, withdrawals, exclusions, or imputation procedures. The registry does not state whether any participants were excluded from the primary analysis after receiving study drug. The primary outcome population is described as participants who received study drug, with a note that a participant may appear in more than one arm.

The record does not report the statistical analysis plan, interim analyses, or sample-size justification. Therefore, it is not possible to assess from the record whether the posted analyses followed a prespecified plan or how missingness and multiplicity were addressed. These omissions matter for interpretation: multiple comparisons can increase the chance of apparently notable findings, while missing outcome data can affect the observed group summaries. Neither concern can be quantified from the posted information.

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 breakdown reports 0 affected participants in every listed MK-1006 and placebo group. No serious adverse event terms are listed. The deaths field is not populated with a count, so deaths are not reported in the registry record; a blank field should not be interpreted as a reported zero.

These serious-event figures are separate from the primary endpoint, which counts participants with at least one adverse event of any type. A serious adverse event is not interchangeable with any adverse event: the broad primary outcome includes events that are not reported as serious. The record's serious-event count therefore does not describe all adverse experiences or their severity distribution.

The other-adverse-event breakdown reports affected participants in several groups. For MK-1006 100 mg, it reports 1 affected participant, while the primary endpoint reports 0 for the same group. The reason for the difference is not reported in the registry record. This discrepancy limits a seamless reading across the two safety summaries and should be made explicit rather than resolved by assumption.

With small and unequal group sizes, zero reported serious events is a descriptive observation, not proof that serious events cannot occur or a precise estimate of their probability. The registry record does not provide confidence intervals or a statistical comparison for serious events.

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

The posted primary results describe how many participants in each dose and placebo group had at least one adverse event during the stated observation period. They show that reported counts were low in most groups, with 3 participants reported in the MK-1006 80 mg group and none in the MK-1006 45 mg and 100 mg groups. A participant with an event is counted once for this endpoint, regardless of whether more than one event occurred.

The results do not establish whether MK-1006 increases, decreases, or leaves unchanged the chance of an adverse event compared with placebo. The registry does not report a formal comparison or uncertainty interval, and participants may contribute to multiple treatment groups. The group sizes also vary. A visual or numerical difference in counts is not, by itself, evidence of a treatment effect.

The counts do not describe the types of events, their duration, severity, timing, or relationship to the study drug. The serious-event breakdown reports zero affected participants in the groups, but the deaths field is not reported. A mismatch between the primary any-event result and the other-adverse-event breakdown is present for the 100 mg group; its cause is not reported.

The study's brief summary frames the primary hypothesis around safety and tolerability assessed through clinical and laboratory evaluations and adverse experiences. The posted primary outcome is one part of that assessment. The record lists pharmacokinetic and pharmacodynamic secondary outcomes, but their results are not reported in the registry record. Thus, no conclusion about those measures can be drawn from the available outcome values.

General statistical explanation: an absence of a reported statistically significant difference is not equivalent to evidence that groups are identical. In this record, a formal comparison is not reported, so even that distinction cannot be evaluated. The result is best understood as a descriptive account of recorded participant counts in a small early-phase study, with uncertainty and design details that are not fully available.

14. Why This Trial Matters Statistically

This trial illustrates why early-phase safety results need to be read at the level of both the count and the group size. A small number of affected participants can look similar across groups while still leaving substantial uncertainty, especially when groups differ in size. The registry's counts are useful as a record of observed events, but they do not substitute for a treatment-effect estimate with uncertainty.

It also highlights the importance of understanding how people contribute to treatment groups. The record labels the design parallel, yet its panel descriptions allow participants to receive both MK-1006 and placebo across treatment periods. The primary outcome description explicitly notes that a participant may appear in more than one arm. That information affects the independence assumptions behind simple comparisons and should accompany any interpretation of group-level counts.

The distinction between any adverse event and a serious adverse event is another key statistical and clinical reporting issue. The primary endpoint is broad, while the serious-event summary addresses a narrower category. Neither should be used as a proxy for the other. The mismatch for the MK-1006 100 mg group further shows why separate outcome records must be checked for internal consistency.

Finally, the registry lists pharmacokinetic and pharmacodynamic questions alongside the safety outcome. Having outcomes listed is not the same as having results available. Separating the existence of a planned or registered measure from its reported numerical findings helps prevent unsupported conclusions. Overall, the record provides descriptive safety counts, but does not report the inferential details needed to quantify comparative precision.

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 available record has limited detail for interpreting the primary results. It does not report a statistical test, confidence intervals, an analysis model, or an adjustment for repeated participation across treatment groups. The registry's parallel-model label coexists with descriptions of multiple treatment periods and possible receipt of both active drug and placebo; the exact allocation and analysis structure is not reported in the registry record.

The groups are unequal in size, and the participant population may overlap across arms. This makes a simple comparison of raw counts especially difficult to interpret. The outcome is a participant count rather than an event count, and no information is reported about the number or nature of events per affected participant. The timeframe is specified, but event timing within that period is not reported.

There is an internal difference in the reported 100 mg safety numbers: the primary endpoint gives 0 affected participants, while the other-adverse-event breakdown gives 1. No explanation is reported. Deaths are not reported in the registry record, and no serious adverse event terms are listed. Neither absence of a term list nor a blank deaths field should be converted into a result that the registry does not state.

Results for the listed pharmacokinetic and pharmacodynamic secondary outcomes are not reported in the registry record. Missing-data procedures, the analysis population beyond the brief outcome description, multiplicity handling, interim analyses, and the original sample-size justification are also not reported. These limitations restrict both the assessment of precision and the ability to judge whether the reported safety pattern reflects a systematic dose relationship.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: MK-1006 Single Dose Study in Japanese Type 2 Diabetes Patients (MK-1006-005) — NCT00791661.
• Registry record last updated 2016-01-07; status last verified 2016-01.
• Results first posted 2012-10-10.
• 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

NCT00791661 is a completed, randomized, double-masked Phase 1 study of single rising doses of MK-1006 in Japanese participants with type 2 diabetes. The registry reports enrollment of 24 and describes placebo comparison across treatment periods. The listed primary endpoint is the number of participants with at least one adverse event during the period from run-in through poststudy follow-up, up to approximately 31 days.

Primary counts are reported for nine MK-1006 dose groups and two placebo groups. Serious adverse events are reported as affecting 0 participants in each group; deaths are not reported in the registry record. The primary and separate safety summaries differ for the MK-1006 100 mg group.

Pharmacokinetic and pharmacodynamic secondary outcomes are listed, but their numerical results are not reported in the registry record. Formal comparisons, confidence intervals, missing-data procedures, and multiplicity handling are also not reported. The posted primary outcome is therefore descriptive and does not establish a comparative treatment effect.