A Study of the Pharmacokinetics of Two Formulations of MK-1006 (MK-1006-010 AM1)(COMPLETED): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Pharmacokinetics of Two Formulations of MK-1006 (MK-1006-010 AM1)(COMPLETED) (NCT00979459), a randomized phase 1 study. The primary outcome is Area Under the Concentration Versus Time Curve (AUC(0-infinity)) for MK-1006.

2. Clinical Question

This is a formulation comparison, not a comparison of MK-1006 with no treatment or with another active drug. The two study conditions differ in how the same stated dose was formulated and administered. The registry describes a single-dose study and identifies pharmacokinetics as its focus.

AUC represents drug exposure over time, while maximum concentration concerns the peak concentration observed after dosing. Although the brief summary names both measures in its hypothesis, only AUC is specified as the primary outcome in the posted endpoint information. A result for maximum concentration is not included among the registry entries reported for the primary endpoint.

The registry identifies the study as randomized and crossover, so the comparison was planned around participants receiving both formulations in different study periods or sequences. The sequence, period details, washout, and the exact participant-level analysis are not reported in the registry record. The results therefore address the recorded pharmacokinetic comparison, but the available information does not establish how all design details were handled in the analysis.

3. Trial Design

The registry identifies NCT00979459 as a completed Phase 1 study with randomized allocation, no masking, and a crossover model. Its title describes a single-dose comparison of two probe formulations of MK-1006. Enrollment is recorded as 12. The study is associated with Type 2 Diabetes and lists Merck Sharp & Dohme LLC as sponsor.

The two study conditions used the same stated 80 mg dose in different forms. The DFC condition was described as a single dose of four 20 mg dry filled capsules. The FCT condition was described as a single dose of two 40 mg film coated tablets. The registry records pharmacokinetic measurements at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96 and 120 hours post-dose.

In a crossover design, participants serve as their own comparison across treatment conditions. As a general statistical principle, this can account for stable differences between participants, but it also makes the analysis dependent on the within-participant comparison and on design features such as sequence and period. The registry record does not report the sequences, the timing or duration of any washout, or a detailed model for the comparison. Those details should not be inferred from the word “crossover.”

The study is marked completed. The registry gives a start of 2009-09 and a primary completion of 2009-11. These dates describe the record’s study timeline, not the timing of each participant’s dosing or follow-up. No further recruitment, protocol, or operational details are reported in the registry record.

The design information supports interpreting the results as a small, randomized, open-label, single-dose pharmacokinetic comparison. It does not by itself establish that the comparison was intended to demonstrate equivalence under a particular margin: the registry labels the posted analysis as non-inferiority or equivalence, but the margin and the full prespecified decision rule are not reported.

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.

First Intervention

7-day Washout Period

Second Intervention

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 Area Under the Concentration Versus Time Curve (AUC(0-infinity)) for MK-1006, measured over Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96 and 120 hours post-dose.

The posted primary endpoint is the area under the concentration-versus-time curve for MK-1006 from zero to infinity, measured in nM*hr. The registry describes AUC as the area under the plasma concentration-time plot for the FCT and DFC formulations. It lists sampling from pre-dose through 120 hours post-dose, with specified measurement times across that interval.

AUC is used in pharmacokinetic comparisons because it represents overall exposure across time, rather than concentration at a single sampling time. As a general explanation, a larger AUC indicates greater measured exposure over the interval represented by the endpoint; the clinical meaning depends on the drug and study context and is not determined by the statistic alone. The endpoint title specifies zero to infinity, while the description refers to the curve from time zero to the last quantifiable concentration. Further computational detail about how the terminal portion was treated is not reported in the registry record.

The posted arm summaries are geometric means: 5171 nM*hr for FCT, with a 95% confidence interval from 4350 to 6147, and 5588 nM*hr for DFC, with a 95% confidence interval from 4593 to 6798. The sponsor’s reported comparison is a geometric mean ratio, which expresses the relationship between the formulations on a ratio scale. AUC is therefore the exposure measure used for the posted primary comparison, while maximum concentration appears in the study summary but does not have a result reported in the endpoint details.

Geometric summaries are commonly used for positive pharmacokinetic measures that may be analyzed on a multiplicative scale. The registry does not report the transformation or detailed analysis method used to obtain these estimates.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports geometric mean AUC by formulation and a geometric mean ratio for the comparison. It does not report a detailed statistical methods section, so the points below distinguish what the posted results contain from general statistical concepts. The precise model, data transformations, handling of missing observations, and decision rule are not reported in the registry record.

What does a geometric mean describe?

As a general statistical explanation, the geometric mean summarizes positive measurements on a multiplicative scale. It can be useful when values are naturally compared as ratios or when the distribution is skewed. A ratio of geometric means compares typical values multiplicatively; it is not an arithmetic difference in the endpoint’s units. The registry reports geometric means for the two arms and a geometric mean ratio, but does not report the detailed computation or the participant-level distribution.

How should the confidence intervals be read?

A confidence interval expresses the uncertainty associated with an estimate under the assumptions of the method used. Narrower intervals generally indicate greater precision, while wider intervals indicate less precision. The two arm-level intervals are 95% intervals for their respective geometric means. The reported 90% interval, 0.86 to 0.99, applies to the geometric mean ratio. Because these intervals refer to different estimands and have different confidence levels, the arm intervals should not substitute for the direct comparative interval.

Confidence intervals are not guarantees that the underlying value lies within the displayed limits, nor are they a direct measure of clinical importance. Their interpretation depends on the model, sampling process, and other analysis assumptions. Those assumptions are not fully described in the registry record.

Why does the crossover design matter?

In a crossover trial, the same participant can contribute observations under both conditions. As a general principle, an analysis can use the within-participant comparison, which may reduce the influence of stable differences between people. The analysis must also account appropriately for features such as treatment sequence and period when relevant. A crossover comparison is not simply two unrelated groups, even when the registry displays separate arm summaries.

The record identifies the design as crossover, but does not report the treatment sequences, washout details, period effects, or the statistical model. It is therefore not possible to determine from the registry information whether or how those features entered the sponsor’s analysis. The arm summaries alone do not reveal the paired data or within-participant variability.

What does an equivalence or non-inferiority label establish?

The registry categorizes the posted ratio analysis as “NON INFERIORITY OR EQUIVALENCE.” In general, an equivalence analysis asks whether an estimate is sufficiently close to a reference under prespecified bounds; a non-inferiority analysis asks whether it excludes an unacceptable disadvantage in a specified direction. Both depend on margins defined before interpreting the result. The registry record does not report the margin, the full hypothesis, or the decision rule. The label therefore identifies the analysis category but is not enough on its own to determine whether the study met a formal criterion.

Neither the p-value nor the analysis method is reported. The absence of those details should not be filled by assuming a standard pharmacokinetic procedure. The 90% confidence interval is part of the posted result, but the registry does not explain how it was constructed.

What can be inferred about precision and sample size?

The enrollment and arm summaries indicate a small study, and the reported confidence intervals are the direct information available about the precision of the posted estimates. No observed-power calculation is reported. General sample-size illustrations based on an observed effect are planning tools rather than evidence that the trial had a particular probability of detecting its observed result. The registry record does not report a sample-size justification or the assumptions used to plan enrollment.

Over-dispersion is a general issue when variation exceeds what a simple statistical model assumes; failing to account for it can make uncertainty estimates misleading. The registry does not provide enough distributional or model information to assess over-dispersion in these data. It also does not report diagnostics or sensitivity analyses.

Overall, the reported summaries permit a descriptive reading of AUC and the sponsor’s ratio estimate. They do not permit reconstruction of the participant-level crossover analysis or a complete independent assessment of its assumptions. Further methodological detail is not reported in the registry record.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s geometric mean ratio as 0.93, with a 90% confidence interval from 0.86 to 0.99, and classifies the analysis as non-inferiority or equivalence. The record also gives geometric mean AUC summaries and 95% confidence intervals for the separate formulations. These are not the same statistic: the ratio is the comparative result, while the arm summaries describe each formulation separately.

No separate recalculated comparative estimate is reported in the registry record. The information available therefore supports describing the sponsor’s posted result, but not setting it beside an independently recalculated contrast. The discrepancy indicator is false, so there is no stated disagreement between a sponsor result and a recalculation that needs to be resolved. The sponsor’s own analysis takes precedence when a discrepancy is present; no such discrepancy is identified in this record.

The ratio and its confidence interval should not be taken as a complete statement of an equivalence or non-inferiority conclusion. The registry does not report the margin, detailed statistical method, or decision rule. Those details are needed to assess the formal interpretation of the sponsor’s analysis. The result can be described precisely as posted, while its decision-level meaning remains limited by the information not reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two secondary outcomes: the number of participants who experienced at least one adverse event and the number who discontinued study medication due to an adverse event. It also reports four outcome measures and two analyses. However, the available outcome details do not provide a result for discontinuation due to an adverse event, and do not give a complete account of all endpoint analyses. That result is not reported in the registry record.

Multiplicity arises when several hypotheses or endpoints are tested. As a general statistical principle, testing multiple outcomes can increase the chance of at least one apparently positive result unless the analysis plan accounts for the family of tests. The registry record does not report whether multiplicity adjustments were planned or used, how the primary and secondary outcomes were ordered, or whether any secondary analyses were confirmatory. No adjustment should be assumed.

The record does not explain whether any participants had missing pharmacokinetic measurements, how missing observations were handled, or whether all randomized participants contributed to each analysis. It also does not specify an analysis population, such as an intention-to-treat or pharmacokinetic evaluable set. These details matter in a crossover study because both treatment-period data and within-participant comparisons may be relevant. The posted summaries do not disclose the participant-level completeness of those data.

Although the registry identifies randomization and a crossover model, it does not report the sequence allocation, protocol deviations, exclusions, or sensitivity analyses. It is therefore not possible to determine whether the posted analysis followed a prespecified plan or whether missingness or exclusions could have affected the comparison. The sponsor’s analysis method and statistical plan are not reported in the registry record.

These omissions do not show that a particular problem occurred. They limit what can be assessed from the posted information: completeness of outcome reporting, control of multiplicity, handling of missing values, and the population represented by the estimates.

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 registry reports zero participants with a serious adverse event in each formulation condition. It reports at least one other adverse event for 7 participants in the FCT condition and 6 in the DFC condition. These are descriptive counts in a study with enrollment of 12; they are not a formal comparative safety analysis.

The registry lists a secondary outcome concerning participants who experienced at least one adverse event. The serious-event counts are shown separately from the counts for other adverse events. The available information does not provide event terms, severity details beyond the serious classification, timing, or an assessment of whether events were considered related to study medication. No deaths are reported as numerical results; death information is not reported in the registry record.

The counts should be read as observations recorded in this particular single-dose study, not as precise estimates of the likelihood of an adverse event in a broader population. With limited enrollment, uncommon events may not be observed. The crossover design also means that the two condition counts should not automatically be treated as results from unrelated groups. The registry does not provide participant-level overlap or a statistical comparison of adverse events.

The registry also names discontinuation due to an adverse event as a secondary outcome, but its results are not included in the registry entries. Therefore, no discontinuation count or conclusion about discontinuation can be drawn from the record.

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

The posted result is a pharmacokinetic comparison of two formulations of MK-1006 after a single 80 mg dose. For AUC, the registry reports geometric means of 5171 nM*hr for FCT and 5588 nM*hr for DFC, with 95% confidence intervals for each arm. The sponsor’s comparative analysis reports a geometric mean ratio of 0.93 and a 90% confidence interval from 0.86 to 0.99.

These figures describe measured drug exposure and uncertainty in this study. They do not by themselves establish a formal finding of equivalence or non-inferiority. The registry does not report the margin or decision rule needed to evaluate that kind of claim. Nor does it provide the detailed statistical method or participant-level results needed to independently reconstruct the crossover analysis.

The record concerns a single dose and a pharmacokinetic endpoint. It does not report clinical outcomes, repeated-dose results, or long-term follow-up. No conclusion about treatment benefit, effectiveness, or clinical outcomes follows from the AUC comparison alone. The registry summary mentions maximum concentration as part of the primary hypothesis, but a maximum-concentration result is not included in the available endpoint details.

The study enrolled 12 and was conducted as a randomized, open-label crossover study. Its scope and precision are consequently limited to the data recorded for this study. The registry does not supply enough participant characteristics to assess applicability across different patient groups, and it does not report a detailed sample-size rationale.

The adverse-event information records zero participants with serious adverse events in either condition and reports other adverse events for 7 participants with FCT and 6 with DFC. These observations are descriptive and do not establish a comparative safety profile. The record does not provide details needed to assess event attribution or to interpret uncommon harms.

In short, the findings characterize the posted AUC results and sponsor ratio for this small single-dose formulation comparison. They leave important questions about the analysis assumptions, formal equivalence criteria, other pharmacokinetic outcomes, and broader clinical interpretation unresolved.

14. Why This Trial Matters Statistically

This trial illustrates why the estimand and scale of a comparison matter. The arm-level results are geometric mean AUC values expressed in nM*hr, while the sponsor’s direct comparison is a geometric mean ratio. The ratio is the result most directly tied to comparing the formulations, and it should not be confused with a difference between arm means.

It also demonstrates the importance of separating confidence intervals for individual arms from the interval for a treatment contrast. The arm intervals describe uncertainty around separate geometric means; the reported 90% interval describes uncertainty around the ratio. A reader needs to know which estimate an interval belongs to before using it to interpret the comparison.

The crossover design makes the within-participant structure important. General statistical reasoning recognizes that observations from the same participant are related. The registry identifies the design but does not report sequence, period, washout, or modeling details. This is a useful reminder that design labels alone do not reveal how the data were analyzed or whether the analysis reflects the intended comparison.

Finally, an equivalence or non-inferiority label is not self-interpreting. The margin and decision rule are central to a formal conclusion, yet they are not reported in this record. The example underscores the value of interpreting the estimate and interval alongside the prespecified criteria, rather than treating a ratio near 1 as sufficient evidence by itself.

These statistical points apply beyond this particular study: distinguish descriptive summaries from comparative estimates, match intervals to their estimands, and identify which design and analysis details are necessary for a defensible conclusion.

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 registry record provides limited detail for assessing the primary analysis. It reports the design, arm summaries, and sponsor ratio, but the statistical method, analysis population, and crossover model are not reported. Sequence allocation, period effects, and washout details are also not reported in the registry record. Without these details, the comparative analysis cannot be reconstructed from the posted summaries.

The registry does not state the equivalence or non-inferiority margin or the formal decision rule, despite classifying the analysis under that category. The p-value is not reported. The record therefore does not support an independent determination of whether a prespecified equivalence or non-inferiority criterion was met.

Enrollment was 12, and there is no reported sample-size justification. The record does not describe the distribution of individual AUC measurements, missing observations, exclusions, protocol deviations, or sensitivity analyses. It also does not explain how incomplete data, if any, were handled. These limitations restrict assessment of precision and robustness beyond the confidence intervals already posted.

The primary endpoint information contains AUC results, but the study summary also refers to maximum concentration. A result for maximum concentration is not reported in the endpoint details. The listed secondary outcome about discontinuation due to an adverse event likewise has no result in the available information. Multiplicity handling is not reported.

Safety reporting is limited to the listed serious and other adverse-event counts. Event descriptions, timing, attribution, and a statistical comparison are not provided. The registry does not report a death count. Finally, the record’s population description is limited to the condition listed as Type 2 Diabetes; broader participant characteristics are not reported. Generalizability beyond this study cannot be assessed from the available record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of the Pharmacokinetics of Two Formulations of MK-1006 (MK-1006-010 AM1)(COMPLETED) — NCT00979459.
• Registry record last updated 2016-02-05; status last verified 2016-02.
• Results first posted 2012-08-20.
• 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

NCT00979459 is a completed Phase 1 randomized, open-label crossover study comparing single 80 mg doses of MK-1006 as a dry filled capsule and a film coated tablet. The registry lists Type 2 Diabetes as the condition and enrollment of 12.

The posted primary endpoint is AUC from zero to infinity, measured in nM*hr. Geometric mean AUC is reported as 5171 for FCT and 5588 for DFC, with 95% confidence intervals of 4350 to 6147 and 4593 to 6798, respectively. The sponsor’s reported geometric mean ratio is 0.93, with a 90% confidence interval from 0.86 to 0.99.

The registry classifies the comparative analysis as non-inferiority or equivalence, but does not report the margin or decision rule. The method, analysis population, and detailed crossover procedures are also not reported in the registry record. Serious adverse events are reported for zero participants in each condition; other adverse events are reported for 7 participants with FCT and 6 with DFC.