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 Pharmacokinetics of MK-3682B in Participants With Moderate to Severe Renal Insufficiency (MK-3682B-030) (NCT02661126), a non-randomized phase 1 study. The primary outcome is Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02661126 |
| Phase | Phase 1 |
| Condition | Hepatitis C |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 16 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants with moderate renal insufficiency, defined by an eGFR of ≥30 mL/min/1.73m^2 to <60 mL/min/1.73m^2, and participants with severe renal insufficiency, defined by an eGFR of ≥15 mL/min/1.73m^2 to <30 mL/min/1.73m^2. Healthy participants with creatinine clearance ≥80 mL/min served as the comparison group. The registry record says healthy participants were matched to participants with renal insufficiency on mean age, BMI, and gender.
Intervention
A single dose of MK-3682B, a fixed-dose combination containing uprifosbuvir, grazoprevir, and ruzasvir. Participants with renal insufficiency took 2 tablets on Day 1 after fasting for 10 hours. The healthy-participant description also specifies 2 tablets after fasting for 10 hours, but records the product name there as MK-362B.
Comparator
Healthy participants were the pharmacokinetic comparison group for participants with moderate or severe renal insufficiency. The study was nonrandomized, and the registry describes matching on mean age, BMI, and gender for the healthy participants. It does not describe a randomized or blinded comparison.
Primary question
How does plasma exposure to uprifosbuvir, measured by AUC0-last, compare between participants with renal insufficiency and healthy participants after a single dose of the fixed-dose combination? The registry record identifies this question and the outcome measure, but numerical AUC results and comparisons are not reported in the registry record.
3. Trial Design
This completed Phase 1 study, NCT02661126, was a two-part, open-label, nonrandomized, parallel study of single-dose pharmacokinetics. The registry lists enrollment of 16 participants and gives the study dates as 2016-01-19 for the start and 2016-08-26 for primary completion. The study concerns MK-3682B, a fixed-dose combination of uprifosbuvir, grazoprevir, and ruzasvir, in the setting of hepatitis C and moderate or severe renal insufficiency.
The described groups were participants with moderate renal insufficiency, participants with severe renal insufficiency, and healthy participants. Renal function categories are defined using eGFR ranges; the healthy group is described using creatinine clearance ≥80 mL/min. The registry says healthy participants were matched to participants with renal insufficiency according to mean age, BMI, and gender. Matching does not make this a randomized comparison: treatment assignment was not randomized, and masking was not used.
Participants received a single dose on Day 1 after fasting for 10 hours. The renal-insufficiency group descriptions specify 2 MK-3682B fixed-dose combination tablets. The healthy-participant description specifies 2 tablets but records the product name as MK-362B, rather than MK-3682B; the registry record does not explain this difference. The primary pharmacokinetic sampling schedule began at pre-dose and continued through 120 hours post-dose, with multiple scheduled measurements during that interval.
The registry describes the primary analysis population as all participants. It does not report the number who contributed evaluable pharmacokinetic measurements, the group sizes for the pharmacokinetic comparisons, or participant flow by renal-function category. It also does not report a detailed statistical analysis plan, sample-size justification, or interim-analysis plan.
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 RI Participants | Healthy Participants |
|---|---|---|
| STARTED | 8 | 8 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants are included in the analysis.
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 RI Participants | Healthy Participants | Total |
|---|---|---|---|---|
| Participants analysed | 8 | 8 | 16 | |
| Age, Continuous | Years | 69.6 (SD 9.0) | 65.8 (SD 2.6) | 67.7 (SD 6.7) |
| Sex: Female, Male: Female | Participants | 2 | 2 | 4 |
| Sex: Female, Male: Male | Participants | 6 | 6 | 12 |
| Body Mass Index (BMI) | kg/m^2 | 30.32 (SD 4.023) | 30.11 (SD 2.057) | 30.22 (SD 3.088) |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682), measured over 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | uM*hr |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the area under the plasma concentration-time curve from dosing to the time of the last measurable concentration, AUC0-last, for uprifosbuvir (MK-3682). It is expressed in uM*hr. In general, an area-under-the-curve measure combines concentration and time information to describe total drug exposure over the observed portion of a concentration-time profile. Here, the endpoint stops at the last quantifiable sample rather than representing a full lifetime exposure estimate.
The registry defines AUC0-last as exposure in plasma from the start of dosing until the last quantifiable sample after oral administration of MK-3682B. Concentrations were scheduled to be measured at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose. The listed endpoint is a pharmacokinetic measure, not a clinical outcome such as symptom change or disease progression.
The registry specifies geometric means and 95% confidence intervals for this endpoint. In general, a confidence interval conveys uncertainty around an estimate; it does not guarantee that the true value lies within the interval. A geometric mean is a summary suited to measurements analyzed on a multiplicative scale. Numerical estimates and confidence intervals for the renal-insufficiency and healthy groups are not reported in the registry record, so the magnitude and precision of the observed exposure estimates cannot be described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies the pharmacokinetic question and endpoint but does not report numerical AUC0-last values, confidence intervals, or comparisons between renal-function groups and healthy participants. Consequently, the posted registry results do not establish the direction, size, or precision of any difference in uprifosbuvir exposure. The absence of numerical results is not evidence that the groups had the same exposure; it means the comparison cannot be interpreted from the registry record.
The primary endpoint is a continuous pharmacokinetic measure summarized by geometric means with 95% confidence intervals. In general, the estimate describes the central exposure level under the chosen summary, while its interval conveys uncertainty in that estimate. To interpret a comparison, readers would need the group-specific estimates and the corresponding comparison or interval. Those numerical details are not reported in the registry record. No p-value or conclusion about statistical significance is reported either.
The design also shapes what a comparison could mean. The study was open-label and nonrandomized, with parallel groups defined by renal function and a healthy comparison group described as matched on mean age, BMI, and gender. Matching on those characteristics does not remove every possible difference between groups, and the registry does not report adjusted estimates or details of any covariate adjustment. The posted record therefore does not support a causal claim that renal insufficiency itself produced a particular change in exposure.
The listed adverse-event figures should be read separately from the primary pharmacokinetic endpoint. They report no serious adverse events among the eight participants listed in the moderate renal-insufficiency group or the eight listed in the healthy group; other adverse events are listed for both groups. These counts do not provide evidence about the unreported pharmacokinetic estimates, and the adverse-event listing does not include a severe renal-insufficiency group.
Overall, the registry record supports a description of the study question, design, endpoint definition, and selected safety counts. It does not provide enough numerical outcome information to quantify pharmacokinetic differences, assess the precision of those differences, or draw a statistical conclusion about them. The study is identified as completed, but completion status does not substitute for posted outcome estimates.
9. Statistical Methods Explained
The statistical information in the registry record is limited. It identifies a geometric-mean summary and 95% confidence interval for the primary pharmacokinetic endpoint, and it says that all participants are included in the analysis. It does not report the numerical endpoint results, the comparison estimates, a detailed model, or the exact procedures used to calculate or compare the group summaries. The explanations below describe general statistical ideas; they should not be read as confirmation that any unreported procedure was used in this study.
What does AUC measure?
In general, the area under a concentration-time curve summarizes exposure over a specified observation interval. AUC0-last uses concentrations from dosing through the last measurable sample. It therefore depends on the measured concentration profile and on which samples are quantifiable. The registry gives the scheduled sampling times through 120 hours after dosing, but does not report the observed profiles, individual AUC values, or how many measurements were below the quantification limit. The endpoint is specific to uprifosbuvir, even though the administered tablet contains a fixed combination of three named components.
Why report a geometric mean?
In general, a geometric mean summarizes positive measurements on a multiplicative scale. It is often useful for pharmacokinetic measures because proportional variation can be more meaningful than differences on an additive scale. A geometric mean should not be interpreted as the arithmetic average of the individual measurements. The registry does not describe the distribution of observed AUC values or provide enough information to assess whether the chosen summary adequately characterizes them.
What does a confidence interval communicate?
In general, a confidence interval expresses uncertainty associated with an estimate under the method used to calculate it. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. It is not a range containing every individual participant's value, and it does not by itself establish whether a difference matters clinically. The registry specifies 95% confidence intervals for the geometric means, but does not report any interval endpoints or a confidence interval for a between-group contrast. Precision therefore cannot be evaluated from the posted results.
Why can renal-function groups be difficult to compare?
In general, nonrandomized groups may differ in characteristics other than the factor used to define them. Matching on mean age, BMI, and gender can improve comparability on those named characteristics, but it does not ensure that all relevant characteristics are balanced. A randomized allocation is not described; allocation is recorded as nonrandomized. The registry does not report adjusted analyses, matching procedures in detail, or an analysis model for group contrasts. Any interpretation must therefore distinguish a descriptive group comparison from a causal effect.
The parallel design means the described groups are separate participant groups rather than repeated renal-function conditions in the same participants. A single-dose pharmacokinetic assessment is the focus. The registry's all-participants analysis-population statement identifies who was intended to be included, but it does not establish that every participant had complete, evaluable concentration measurements. The handling of missing samples and nonquantifiable concentrations is not reported in the registry record.
How should planning illustrations be read?
In general, a sample-size calculation estimates how many participants or events a hypothetical design would require under stated assumptions. It is a planning exercise, not a measure of the probability that a completed study found an effect. The planning description associated with this study states a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. The specific planning outputs and effect fractions are not reported in the registry record. These assumptions should not be mistaken for the trial's original design justification; that justification is not reported in the registry record. A planning calculation based on an observed effect also does not turn the result into observed power.
For outcomes that are not time-to-event outcomes, planning quantities are described as participants per arm; for time-to-event outcomes, the planning description refers to total events. These conventions explain what a planning quantity would represent, not what was actually enrolled or observed. The study's reported enrollment is 16, while the adverse-event listings identify 8 participants in each of two groups. The registry does not provide the severe-group safety listing or enough group-specific pharmacokinetic counts to reconcile all participant flow.
Multiplicity concerns arise when multiple outcomes or comparisons are examined. In general, making many statistical tests can increase the chance of at least one nominally significant finding if no adjustment or other strategy is used. The registry lists 42 outcome measures and 24 analyses, but does not report a multiplicity adjustment strategy or explain how the primary endpoint was prioritized relative to other analyses. Those counts alone do not reveal how many distinct hypotheses were tested or how their results were interpreted.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies AUC0-last of uprifosbuvir as the primary outcome and states that all participants are included in its analysis. It also lists 42 outcome measures and 24 analyses. Those counts indicate that the record contains multiple outcomes and analyses, but they do not by themselves establish how many statistical hypotheses were tested, which comparisons were considered confirmatory, or whether any adjustment was applied. A multiplicity strategy is not reported in the registry record.
Missing-data handling is not reported in the registry record. The all-participants analysis-population description does not show whether all participants had complete concentration profiles, whether some samples were unavailable or below the lower limit of quantification, or how incomplete profiles were handled. Nor does the record describe exclusions from pharmacokinetic analyses or sensitivity analyses for missing measurements.
The primary endpoint definition uses the last quantifiable concentration, and the registry lists scheduled measurements through 120 hours post-dose. This definition identifies the measurement interval in principle, but does not disclose participant-level completeness or the number of quantifiable samples. The posted record also does not report the detailed statistical model or any adjustment for the nonrandomized group structure. These omissions limit assessment of how robust the reported analysis would be, even though numerical pharmacokinetic results are not reported either.
As a result, the registry record allows identification of the stated primary outcome and broad analysis population, but not an assessment of multiplicity control, missing-data assumptions, or the handling of incomplete concentration-time profiles.
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 RI Participants | 0 | 8 | 0.0% |
| Healthy Participants | 0 | 8 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Moderate RI Participants | 0 of 8 |
| Healthy Participants | 0 of 8 |
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 RI Participants | 2 of 8 |
| Healthy Participants | 1 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Moderate RI Participants | Healthy Participants |
|---|---|---|---|
| Vomiting | Gastrointestinal disorders | 1 of 8 | 1 of 8 |
| Headache | Nervous system disorders | 2 of 8 | 0 of 8 |
| Nausea | Gastrointestinal disorders | 1 of 8 | 0 of 8 |
The registry lists serious adverse events for the moderate renal-insufficiency group and the healthy group. In each listed group, 0 of 8 participants had a serious adverse event, and no deaths are listed. Other adverse events are reported for 2 of 8 participants in the moderate group and 1 of 8 participants in the healthy group. These are counts, not estimates of comparative risk, and no statistical comparison is reported.
The safety listing does not include a severe renal-insufficiency group, although severe renal insufficiency is described as part of the study. Severe-group serious and other adverse-event figures are not reported in the registry record. The registry also does not provide event descriptions for the other adverse events in the listing, their timing, severity, relationship to treatment, or whether participants experienced more than one event.
Zero serious events in the listed groups means none were recorded among the participants counted in those groups; it does not prove that the risk of a serious event is absent. These safety counts are limited in scope and should not be treated as a substitute for the pharmacokinetic results, which are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
This study was designed to describe single-dose pharmacokinetics of a fixed-dose combination in participants with moderate or severe renal insufficiency and compare those observations with a healthy group. Its primary endpoint focuses on uprifosbuvir exposure, measured as AUC0-last. This makes the study question specific: it concerns plasma exposure over the observed sampling interval, not every possible effect of the combination or a clinical outcome.
The registry record does not report numerical AUC estimates, confidence intervals, or group contrasts. It therefore does not show whether exposure was higher, lower, or similar across the described groups, nor how precisely any such comparison was estimated. No conclusion about the direction or size of a pharmacokinetic difference can be recovered from the endpoint definition alone.
The design is nonrandomized and open-label. Healthy participants were described as matched on mean age, BMI, and gender, but matching does not create random allocation or guarantee comparability on unlisted characteristics. The registry does not report adjusted comparisons. Any available group contrast would consequently need to be interpreted as an observed comparison in this study rather than automatically as a causal effect of renal insufficiency.
The record identifies a completed Phase 1 study with enrollment of 16. Its safety listing reports zero serious adverse events in the moderate and healthy groups shown, along with other adverse-event counts; severe-group safety figures are not reported in the registry record. These limited counts do not establish broader safety conclusions.
In general, a pharmacokinetic study can characterize exposure under a specified dose and sampling schedule, but the registry information alone does not answer whether a clinical outcome changes. The record does not report the numerical pharmacokinetic results, detailed methods for missing measurements, multiplicity handling, or a sample-size justification. The appropriate statistical reading is therefore descriptive: the study question and measurement plan are identifiable, but the posted numerical evidence needed to interpret the primary comparison is not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable because it frames renal function as the basis for comparing single-dose pharmacokinetic profiles, while using a nonrandomized parallel design. For clinical researchers, that distinction matters: group summaries may describe exposure patterns, but nonrandomized comparisons require caution about differences between groups beyond the characteristics used for matching. The registry says matching considered mean age, BMI, and gender; it does not report further matching details or an adjusted comparison model.
The endpoint also illustrates a common feature of pharmacokinetic analysis. AUC0-last summarizes exposure only through the last measurable sample, and the registry defines the measure and scheduled sampling times. The choice of a geometric mean and confidence interval indicates an intended summary of both central exposure and its uncertainty. Without the actual estimates and intervals, however, neither the size of exposure nor the precision of the comparison can be evaluated.
The record distinguishes the planned primary endpoint from a clinical endpoint. AUC0-last is a drug-exposure measure, so it addresses pharmacokinetics rather than whether participants experienced a clinical benefit. This distinction is important when interpreting a Phase 1 study: the measurement question is narrow, and it should not be expanded beyond the outcomes reported.
Finally, the record highlights why completeness of reporting matters. It specifies an analysis population and displays selected adverse-event counts, but does not report numerical primary pharmacokinetic results, missing-data handling, or multiplicity methods. Statistical interpretation depends not only on the design and endpoint definitions, but also on the estimates, their uncertainty, and the methods used to obtain them. Those elements are not reported in the registry record.
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 important limitation for statistical interpretation is that numerical results for the primary pharmacokinetic endpoint are not reported in the registry record. Without group estimates, confidence intervals, and comparison results, readers cannot assess the magnitude, direction, or precision of any exposure contrast. Completion status and the endpoint definition do not fill this gap.
The nonrandomized, open-label design limits causal interpretation. The healthy group is described as matched on mean age, BMI, and gender, but the registry does not detail the matching method, report balance on other characteristics, or identify an adjusted analysis. The record also does not report how the moderate and severe groups were compared with healthy participants.
There is a discrepancy in the healthy-participant intervention description: it names 2 MK-362B FDC tablets, while the study and other arm descriptions name MK-3682B. The registry record does not explain this difference. It also describes severe renal insufficiency as a study group but does not include that group in the adverse-event listing. Severe-group safety counts are not reported in the registry record.
Further limitations include the absence of reported missing-data procedures, detailed handling of nonquantifiable concentrations, multiplicity methods, and a statistical model. The record states that all participants are included in the primary analysis, but does not report the number with complete pharmacokinetic profiles. The sample-size justification and interim-analysis plan are not reported in the registry record. Together, these gaps limit independent assessment of the analysis and its precision.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics of MK-3682B in Participants With Moderate to Severe Renal Insufficiency (MK-3682B-030) — NCT02661126.
- Registry record last updated 2019-01-09; status last verified 2018-12.
- Results first posted 2018-12-14.
- 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
NCT02661126 is a completed, open-label, nonrandomized Phase 1 study of single-dose MK-3682B pharmacokinetics in participants with moderate or severe renal insufficiency, with healthy participants as a comparison group. The registry reports enrollment of 16 and describes fasting administration on Day 1. Healthy participants were described as matched on mean age, BMI, and gender.
The primary outcome is uprifosbuvir AUC0-last, summarized as a geometric mean with a 95% confidence interval. Numerical primary outcome results and group comparisons are not reported in the registry record. The adverse-event listing includes moderate renal-insufficiency and healthy groups, with no serious adverse events or deaths listed in either; severe-group safety figures are not reported. The record does not report detailed missing-data, multiplicity, or model specifications.