This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Assessment of Pharmacokinetics of Single Dose Odanacatib (MK-0822) in Participants With Moderate Hepatic Insufficiency (MK-0822-070) (NCT01512693), a non-randomized phase 1 study. The primary outcome is Area Under the Concentration-time Curve of MK-0822 From Time 0 to Infinity (AUC0-∞) After Single Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01512693 |
| Phase | Phase 1 |
| Condition | Hepatic Insufficiency |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 17 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants with moderate hepatic insufficiency and healthy matched control participants. The study enrolled 17 participants overall. The registry record does not report the number in each group for the primary endpoint analysis.
Intervention
A single oral dose of odanacatib, also identified as MK-0822, at 50 mg. Both groups received the same stated dose; the comparison concerns pharmacokinetics in different participant groups, not different treatments.
Comparator
Healthy matched control participants who also received a single 50 mg dose. The study was non-randomized and open-label, so the groups were not formed by randomized assignment.
Primary question
How does total plasma exposure to odanacatib, measured by AUC0-∞, compare between participants with moderate hepatic insufficiency and healthy matched controls after one dose? The stated primary hypothesis is that the AUC0-∞ values are similar.
This is a pharmacokinetic question: it concerns the concentration of a drug in plasma over time, rather than a clinical outcome such as symptom improvement. The primary endpoint is described as total drug exposure, and blood samples were scheduled from predose through 336 hours after dosing. The registry record identifies the primary measure and its confidence-interval format, but does not report the group estimates, the confidence interval limits, or a numerical comparison. Therefore, the registry record does not establish how close the group results were or how precisely their difference was estimated.
The stated aim was to assess whether moderate hepatic insufficiency may affect odanacatib exposure. The comparison is between people with different hepatic status, not between people assigned at random to two interventions. Matching is noted in the control-group description, but the matching factors and procedures are not reported in the registry record. The primary hypothesis uses the term “similar”; a prespecified numerical criterion for deciding similarity is not reported in the registry record.
3. Trial Design
This completed Phase 1 study was an open-label, non-randomized, parallel-group comparison. It enrolled 17 participants and compared a moderate hepatic insufficiency group with a healthy matched control group. Participants in both groups received one 50 mg dose of odanacatib (MK-0822). The registry record lists Hepatic Insufficiency as the condition and Merck Sharp & Dohme LLC as the sponsor.
The study began on 2012-02-23 and reached primary completion on 2012-04-24. Its status is recorded as completed. These dates describe the study timeline; they do not indicate when every participant was assessed or when all analyses were completed. The participant flow, reasons for any exclusions, and the number included in each endpoint analysis are not reported in the registry record.
In a parallel-group design, participants belong to one group for the comparison rather than crossing over between conditions. Here, the groups are defined by hepatic status, and both receive the same single dose. Because allocation was non-randomized, the comparison is not protected by random assignment against baseline differences between groups. The registry record calls the healthy participants matched controls, but does not identify the matching variables or explain how matching was carried out. Consequently, the extent to which the groups were comparable on measured or unmeasured characteristics cannot be assessed from the registry record.
Masking is listed as none. This is consistent with an open-label study, in which treatment assignment is not concealed from participants and study personnel. The study description focuses on plasma pharmacokinetics and names AUC0-∞ as the primary endpoint. Secondary outcomes include maximum concentration (Cmax), time to maximum concentration (Tmax), and apparent terminal half-life (t1/2). Details of the statistical model, covariate adjustment, or the handling of values that could not be measured are not reported in the registry record.
The primary endpoint population is described as the per-protocol population: participants who complied sufficiently with the protocol for results to be expected to reflect the effects of treatment under the underlying scientific model. The actual size and composition of that population are not reported in the registry record. The safety figures use their own at-risk counts, which should not be assumed to equal the endpoint-analysis population.
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.
Overall Study
| Stage | Moderate Hepatic Insufficiency Group | Healthy Matched Control Group |
|---|---|---|
| STARTED | 8 | 9 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Moderate Hepatic Insufficiency Group | Healthy Matched Control Group |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The per protocol population consisted of all participants who complied with the protocol sufficiently to ensure that results will likely exhibit the effects of treatment according to the underlying scientific model.
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.
| Characteristic | Unit | Moderate Hepatic Insufficiency Group | Healthy Matched Control Group | Total |
|---|---|---|---|---|
| Participants analysed | 8 | 9 | 17 | |
| Age, Continuous | years | 53.1 (SD 4.9) | 54.2 (SD 5.3) | 53.7 (SD 5.0) |
| Sex: Female, Male: Female | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 7 | 8 | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Concentration-time Curve of MK-0822 From Time 0 to Infinity (AUC0-∞) After Single Dose, measured over Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | μM*hr |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the area under the plasma concentration-time curve from time 0 to infinity, abbreviated AUC0-∞, after a single dose of odanacatib. It is reported in μM*hr, with least-squares means and a 95% confidence interval specified in the registry record. Plasma samples were scheduled at predose and at 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose. The stated timeframe describes the sampling schedule, not the timing of a clinical benefit.
AUC represents the accumulated concentration of a drug in plasma over time. AUC0-∞ includes estimated exposure beyond the last observed sample, extending the measured concentration-time profile to infinity. In general, this endpoint is used in pharmacokinetic studies because it summarizes overall systemic exposure rather than focusing on a single concentration or time point. Cmax, listed as a secondary outcome, concerns the maximum concentration; Tmax concerns when that maximum occurs; and apparent terminal half-life describes the terminal decline in concentration.
The primary endpoint description states that AUC0-∞ is a measure of total drug exposure. The stated comparison asks whether exposure is similar between participants with moderate hepatic insufficiency and healthy matched controls. The group least-squares means and 95% confidence intervals are not reported in the registry record, nor are the numerical contrast, its confidence interval, or a threshold defining similarity. Thus, the endpoint and intended comparison are identifiable, but the magnitude and precision of the observed comparison cannot be interpreted from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a focused pharmacokinetic comparison: AUC0-∞ after a single 50 mg dose of odanacatib in participants with moderate hepatic insufficiency versus healthy matched controls. It describes the endpoint as a least-squares mean with a 95% confidence interval. However, it does not report the group estimates or confidence limits. Without those values, the direction, size, and precision of the observed exposure comparison cannot be described. The registry record therefore does not support a conclusion about whether the groups had similar AUC0-∞ values.
A confidence interval is a range of values compatible with the data and the statistical procedure used, under its assumptions. In general, a narrower interval indicates greater precision, while a wider interval indicates more uncertainty about the estimated quantity. The interval is not reported in the registry record, so its width and the degree of uncertainty are unknown. A p-value for the primary comparison is also not reported in the registry record. No significance claim can be made from the endpoint description alone.
The hypothesis that exposure is “similar” is not, by itself, a numerical decision rule. A formal equivalence interpretation generally depends on a prespecified margin defining how much difference would still count as sufficiently similar, along with an appropriate comparison and interval assessment. Such a margin and its rationale are not reported in the registry record. The absence of a reported margin does not establish that none was used; it means the registry record does not document one.
The comparison is non-randomized. In general, non-randomized groups may differ in characteristics beyond the group-defining condition, and statistical adjustment or matching can address only characteristics that are measured and handled appropriately. The registry record identifies healthy matched controls but does not report matching factors, baseline characteristics, or adjustment details. This limits assessment of how well group differences were controlled.
The total enrollment was 17, but the number included in the primary endpoint analysis is not reported in the registry record. The listed per-protocol population definition does not state how many participants met it. The safety at-risk counts are reported separately and do not establish the endpoint-analysis sample size. Overall, the record supports describing the study question and design, but not the numerical result or its certainty.
9. Statistical Methods Explained
The primary measure is continuous: AUC0-∞ is a quantity on a numerical scale, expressed in μM*hr. The registry record specifies least-squares means and 95% confidence intervals. A least-squares mean is generally a model-based mean, potentially adjusted for terms included in the statistical model. The model terms, any covariates, and the exact procedure used to estimate the means are not reported in the registry record. It is therefore not possible to determine from the record whether the reported estimand was adjusted or how the estimates were calculated.
What does a confidence interval contribute?
In general, a confidence interval communicates the precision of an estimate by giving a range of values compatible with the observed data under the specified method and its assumptions. It is not a guarantee that the true value lies in the interval, and its interpretation depends on the analysis procedure. For a comparison of groups, the interval for the contrast is especially useful because it shows which sizes and directions of difference remain compatible with the data. The registry record specifies 95% confidence intervals for the endpoint but does not report their limits or clarify whether these apply to each group mean, the between-group contrast, or both.
A point estimate without an interval can give an incomplete account, because it does not show how much uncertainty surrounds the estimate. Conversely, an interval without a clear estimand can also be difficult to interpret. For this study, the named endpoint is total exposure and the intended groups are clear, but the numerical estimates, contrast, interval limits, and detailed model are not reported in the registry record. As a result, neither the estimated magnitude nor its precision can be evaluated.
How should the similarity hypothesis be assessed?
In general, failure to find evidence of a difference is not the same as evidence that two groups are sufficiently similar. A similarity or equivalence claim requires a defined range of differences regarded as unimportant for the question, chosen before examining the results, and an analysis that evaluates the estimate against that range. The registry record states that the primary hypothesis is that AUC0-∞ is similar between groups, but does not report a numerical similarity or equivalence margin. It also does not report the primary comparison estimate or confidence interval. The stated hypothesis can therefore be described, but its statistical evaluation cannot be reconstructed from the record.
The record identifies a 95% confidence interval but does not report a p-value for the primary endpoint. In general, p-values and confidence intervals answer related but distinct questions: a p-value assesses compatibility with a specified null hypothesis under a test, while an interval conveys a range of estimates compatible with the data and method. Neither substitutes for stating the magnitude of the effect or the criterion relevant to the scientific question. A p-value alone would also not establish similarity. No specific test, null hypothesis, or decision rule is reported in the registry record.
What are the design implications?
The parallel-group comparison contrasts participants with moderate hepatic insufficiency against healthy matched controls, with both groups receiving a single dose. In general, non-randomized comparisons can be influenced by differences between groups other than the characteristic under study. Matching may improve comparability for the factors used in matching, but the matched factors and procedures are not reported in the registry record. It is also not clear whether the analysis accounted for any matching in its model. The record does not describe covariate adjustment or sensitivity analyses.
Open-label status means masking was not used. For a laboratory concentration measurement, lack of masking may be less directly tied to subjective assessment than it would be for an outcome requiring judgment, but it does not remove other possible sources of bias or uncertainty. This is a general methodological observation, not a claim about bias in this study. The registry record does not describe laboratory blinding, assay procedures, or quality-control methods.
The endpoint population is defined as per protocol, based on adequate protocol compliance. In general, a per-protocol analysis may exclude participants who do not meet specified requirements, so its interpretation depends on the eligibility and exclusion rules and the resulting participant count. Those rules beyond the general definition, the number analyzed, and the reasons for exclusions are not reported in the registry record. The enrollment of 17 should not be substituted for the unreported endpoint-analysis size.
The record lists four outcome measures and two analyses, but does not describe which analyses correspond to which outcomes or give a full statistical analysis plan. A retrospective planning illustration is described as using the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. For non-time-to-event outcomes, such planning illustrations are expressed as participants per arm. Such calculations are planning illustrations, not observed power and not evidence that the original trial was designed with those assumptions. Numerical planning results are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies one primary outcome, AUC0-∞, and three secondary outcomes: Cmax, Tmax, and apparent terminal half-life. It also reports four outcome measures and two analyses. The relationship between the listed outcomes and analyses, and whether any multiplicity adjustment or prespecified hierarchy was used, are not reported in the registry record. In general, when multiple outcomes or comparisons are examined, the chance of at least one apparently notable result can increase unless the analysis plan addresses multiplicity. Whether that issue applies to a particular conclusion depends on the planned inferential framework and cannot be determined from the outcome list alone.
The record describes the primary analysis population as per protocol and gives a general definition based on sufficient protocol compliance. It does not report the number of participants in that population, group-specific endpoint-analysis counts, or details of how participants were classified. The 17 enrolled participants and the safety at-risk counts do not establish the number contributing to the primary endpoint analysis.
Missing-data handling is not reported in the registry record. This includes whether any AUC values were unavailable, how incomplete concentration profiles were handled, and whether any imputation or sensitivity analysis was planned or performed. In general, missingness can affect an estimate when the availability of measurements is related to participant characteristics or outcomes. Its possible impact depends on why data are missing and how the analysis addresses them; neither is documented in the registry record.
The exact statistical analysis plan, including the test for the primary comparison, treatment of multiplicity, and analysis of missing data, is not reported in the registry record. The presence of a stated endpoint and confidence-interval format does not fill in those details.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Moderate Hepatic Insufficiency Group | 0 | 8 | 0.0% |
| Healthy Matched Control Group | 0 | 9 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Moderate Hepatic Insufficiency Group | 1 of 8 |
| Healthy Matched Control Group | 1 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Moderate Hepatic Insufficiency Group | Healthy Matched Control Group |
|---|---|---|---|
| Nasopharynigitis | Infections and infestations | 1 of 8 | 0 of 9 |
| Headache | Nervous system disorders | 0 of 8 | 1 of 9 |
The registry record reports serious adverse events for both groups. In the moderate hepatic insufficiency group, 0 of 8 participants at risk were reported with a serious adverse event; in the healthy matched control group, 0 of 9 were reported with a serious adverse event. These are counts for the groups and at-risk numbers recorded for this safety outcome. They do not establish that no adverse events of any kind occurred.
For the broader “other adverse events” category, 1 of 8 participants at risk in the moderate hepatic insufficiency group and 1 of 9 in the healthy matched control group were reported as affected. The registry record does not name the events in the posted safety summary. The list of top serious-event terms is empty. Death counts are recorded as null, which means they are not reported in the registry record; null should not be interpreted as zero deaths.
These figures are descriptive counts from a small study. In general, counts of events do not on their own establish that one group has greater or lower risk, particularly when group sizes are limited and assignment is not randomized. The safety figures also do not describe severity, timing, duration, or relationship to treatment beyond the categories recorded. Those details are not reported in the registry record. The counts should be read as the recorded safety summaries, not as proof that other events could not have occurred or as a comparative safety conclusion.
12. What the Result Does, and Does Not, Mean
The record establishes that the study was designed to compare total plasma exposure to odanacatib after one 50 mg dose in participants with moderate hepatic insufficiency and healthy matched controls. It identifies AUC0-∞ as the primary pharmacokinetic endpoint and states that the intended hypothesis was similarity between groups. The record also describes the sampling schedule and specifies least-squares means with 95% confidence intervals as the endpoint summary format.
However, the primary endpoint estimates and confidence limits are not reported in the registry record. The numerical group comparison therefore cannot be characterized as showing higher, lower, or similar exposure, and its precision cannot be assessed. The record also does not provide a numerical similarity margin or the detailed statistical plan needed to evaluate the stated hypothesis. A study question is not itself a study result, and an endpoint definition does not establish what the measurements showed.
This is a single-dose pharmacokinetic comparison, not a reported evaluation of clinical benefit. AUC0-∞ describes drug exposure in plasma; it does not directly measure whether participants experienced an improvement in health. The registry record lists secondary pharmacokinetic measures, but their numerical results are also not included in the information available in the registry record. No conclusion about clinical effects follows from the endpoint description alone.
The study’s non-randomized design also matters when interpreting a group comparison. The healthy participants are described as matched controls, but the matching factors and baseline group characteristics are not reported. Consequently, the record does not show how fully the groups were comparable apart from hepatic status. The per-protocol population is defined, but its size and the number analyzed are not reported.
The safety summaries record no serious adverse events among the participants at risk in either group and one participant affected by other adverse events in each group. Those small descriptive counts do not establish a comparative safety profile. Taken together, the registry record provides the rationale, design, endpoint definition, and selected safety counts, but does not report enough outcome detail to determine the primary pharmacokinetic result.
13. Why This Trial Matters Statistically
This study illustrates a common pharmacokinetic question: whether a health condition may be associated with a change in systemic exposure after a drug dose. AUC0-∞ is useful for that purpose because it summarizes concentration over time rather than relying on a single blood sample. The distinction between total exposure, peak concentration, time to peak, and terminal half-life also shows why several pharmacokinetic measures can be informative while answering different questions.
The study also illustrates the importance of matching the claim to the design. Participants were not randomized to hepatic-status groups. The comparison can describe observed pharmacokinetic measurements, but non-randomized group membership means that other differences between participants may complicate interpretation. The registry record calls the controls matched but does not state which factors were matched, so the extent of comparability cannot be judged from the record.
Precision is central to interpreting a similarity question. A stated intention to find similar exposure does not show that similarity was demonstrated. The group estimates, confidence intervals, and any numerical margin used to define similarity are needed to assess how large a difference remains plausible and whether it falls within a meaningful range. Those result details are not reported in the registry record.
The enrollment of 17 is a reminder that the number enrolled and the number included in a particular analysis are not necessarily the same. The primary population is described as per protocol, but its actual size is not reported. Safety at-risk counts are available, yet they should not be treated as the endpoint-analysis counts. In general, transparent reporting of participant flow, analysis populations, uncertainty, and missing-data handling helps readers distinguish an imprecise estimate from a precise one and understand the scope of a result.
The registry record therefore makes the scientific question and intended endpoint clear, while leaving the key numerical answer unavailable. That gap is statistically important: without estimates and uncertainty, the comparison cannot be evaluated for magnitude, precision, or compatibility with the stated similarity hypothesis.
14. 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 most direct limitation for interpreting this study is that the registry record does not report the primary endpoint estimates or their 95% confidence intervals. It therefore does not show the size or direction of the AUC0-∞ comparison, or how precisely it was estimated. Numerical results for the secondary pharmacokinetic measures are not included in the registry record either.
The study is non-randomized and open-label. The registry record describes the control participants as matched, but matching factors, matching procedures, and baseline characteristics are not reported. The extent to which the groups differed in other measured or unmeasured characteristics cannot therefore be assessed. The statistical model and any adjustment for those characteristics are also not reported in the registry record.
The endpoint population is defined as per protocol, but the number of participants included in that analysis and the reasons for any exclusions are not reported. The total enrollment and safety at-risk counts do not fill that gap. Details on missing concentration measurements, incomplete profiles, and missing-data methods are also not reported. These omissions limit assessment of the analyzed population and the potential influence of unavailable measurements.
The stated hypothesis uses the concept of similarity, but a numerical margin defining similarity is not reported in the registry record. The analysis method, test, and any multiplicity strategy are also not described. Without these details and the endpoint results, the statistical evaluation of the primary hypothesis cannot be reconstructed.
Finally, the study concerns a single 50 mg dose and a pharmacokinetic endpoint. Its stated design does not answer questions about repeated dosing or clinical outcomes. Those are limits on the scope of the study question, not conclusions about what would occur in other settings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Assessment of Pharmacokinetics of Single Dose Odanacatib (MK-0822) in Participants With Moderate Hepatic Insufficiency (MK-0822-070) — NCT01512693.
- Registry record last updated 2018-08-29; status last verified 2018-07.
- Results first posted 2017-10-27.
- 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.
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18. Record Summary
This completed Phase 1 study compared pharmacokinetics after a single 50 mg dose of odanacatib (MK-0822) in participants with moderate hepatic insufficiency and healthy matched controls. The study was open-label, non-randomized, and parallel-group, with total enrollment of 17. It began on 2012-02-23 and reached primary completion on 2012-04-24.
The primary endpoint was AUC0-∞, a measure of total plasma drug exposure, specified as a least-squares mean with a 95% confidence interval. Secondary measures were Cmax, Tmax, and apparent terminal half-life. The registry record does not report numerical estimates or confidence limits for the primary endpoint, the endpoint-analysis sample size, or the detailed statistical plan.
For safety, no serious adverse events were recorded among 8 participants at risk in the moderate hepatic insufficiency group or 9 in the healthy matched control group. One participant in each group was affected by other adverse events. Death counts are not reported in the registry record.