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 Study to Evaluate MK-6096 in the Treatment of Painful Diabetic Neuropathy (PDN) in Adults (MK-6096-021) (NCT01564459), a randomized phase 2 study. The primary outcome is Time to Efficacy Failure (TTEF) - Primary Responders.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01564459 |
| Phase | Phase 2 |
| Condition | Diabetic Neuropathy, Painful |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 170 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Adults with painful diabetic neuropathy were the intended study population. For the primary endpoint, however, the analysis population was narrower: participants randomized and continued into the double-blind treatment period who met the study definition of a primary responder.
Intervention
The intervention was MK-6096 10 mg once daily. Participants received it during a 1-week run-in; the active-treatment group continued MK-6096 once daily during the double-blind period.
Comparator
The comparator was placebo once daily during the double-blind period. Participants in this group also received MK-6096 10 mg once daily during the 1-week run-in.
Primary question
Among primary responders who continued into double-blind treatment, how long did it take for a documented efficacy failure to occur in the MK-6096 group compared with the placebo group? The registry record identifies this as time to efficacy failure, but does not report the group median estimates or confidence intervals.
The trial therefore addresses a specific question about maintenance of an initial pain response, rather than a question about pain change across every randomized participant. A primary responder was defined by a decrease of at least 30% in treatment baseline pain relative to run-in baseline pain. The primary outcome then tracked time until a predefined worsening pattern met the efficacy-failure criteria.
This distinction matters for interpretation. The endpoint concerns participants who first met a response threshold and continued into the double-blind period. It does not directly summarize the chance of becoming a responder among all participants, nor does it describe outcomes for people who did not meet that responder definition. The registry record does not report how many participants were excluded from this endpoint population or why. It also does not report a numerical estimate of the between-group difference in time to failure.
3. Trial Design
This was a phase IIa, randomized, triple-masked, parallel-group, placebo-controlled trial in adults with painful diabetic neuropathy. The registry record lists enrollment of 170. The study start date was 2012-03-26, primary completion was 2013-04-18, and the status is completed. Merck Sharp & Dohme LLC is listed as the sponsor.
Both groups received MK-6096 10 mg once daily during a 1-week run-in. During the double-blind treatment period, one group continued MK-6096 10 mg once daily for 2 weeks and the other received placebo once daily for 2 weeks. Thus, the double-blind comparison followed a common active-drug run-in rather than starting the two groups on different treatments from the outset.
The primary endpoint’s stated timeframe begins on Day 1 of the double-blind treatment phase and extends up to 28 days. The arm descriptions specify a 2-week double-blind treatment period. The registry record does not explain the difference between the stated treatment duration and the endpoint timeframe, so the timing cannot be reconciled from the record alone.
The primary analysis population consisted of randomized participants who continued into double-blind treatment and met the primary-responder definition. The posted group counts for this endpoint are 37 for MK-6096 and 28 for placebo. Those are endpoint group counts, not the overall enrollment figures. The registry record does not provide a complete account of participant flow from enrollment through the endpoint analysis.
A randomized, masked, parallel-group design can support a controlled comparison by assigning participants to concurrent treatment groups while limiting some influences on assessment. Those design features do not by themselves establish that a difference occurred or that an estimate is precise. In this record, the primary outcome’s median estimates and confidence intervals are not reported, which prevents a quantitative reading of the planned comparison.
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.
Run-In
| Stage | MK-6096 10 mg→No Treatment | MK-6096 10 mg→MK-6096 10 mg | MK-6096 10 mg→Placebo |
|---|---|---|---|
| STARTED | 12 | 87 | 83 |
| COMPLETED | 0 | 87 | 83 |
| NOT COMPLETED | 12 | 0 | 0 |
Reasons for not completing this period:
| Reason | MK-6096 10 mg→No Treatment | MK-6096 10 mg→MK-6096 10 mg | MK-6096 10 mg→Placebo |
|---|---|---|---|
| Adverse Event | 7 | 0 | 0 |
| Lost to Follow-up | 1 | 0 | 0 |
| Non-compliance with study drug | 2 | 0 | 0 |
| Protocol Violation | 1 | 0 | 0 |
| Withdrawal by Subject | 1 | 0 | 0 |
Double-blind Treatment
| Stage | MK-6096 10 mg→No Treatment | MK-6096 10 mg→MK-6096 10 mg | MK-6096 10 mg→Placebo |
|---|---|---|---|
| STARTED | 0 | 87 | 83 |
| COMPLETED | 0 | 87 | 82 |
| NOT COMPLETED | 0 | 0 | 1 |
Reasons for not completing this period:
| Reason | MK-6096 10 mg→No Treatment | MK-6096 10 mg→MK-6096 10 mg | MK-6096 10 mg→Placebo |
|---|---|---|---|
| Adverse Event | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: All randomized participants (continued into double-blind treatment period) who met criteria as a primary responder.
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 | MK-6096 10 mg→No Treatment | MK-6096 10 mg→MK-6096 10 mg | MK-6096 10 mg→Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 12 | 87 | 83 | 182 | |
| Age, Continuous | years | 54.8 (SD 6.9) | 55.6 (SD 9.2) | 55.5 (SD 10.3) | 55.5 (SD 9.5) |
| Sex: Female, Male: Female | Participants | 7 | 38 | 36 | 81 |
| Sex: Female, Male: Male | Participants | 5 | 49 | 47 | 101 |
6. Primary Endpoint
The registry lists the primary outcome as Time to Efficacy Failure (TTEF) - Primary Responders, measured over Day 1 of double-blind treatment phase to the first documented efficacy failure (up to 28 days).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint was time to efficacy failure among primary responders. Participants rated pain twice daily on a scale from 0 to 10, where 0 meant no pain and 10 meant the worst pain imaginable. The average evening pain scores over the last 3 days of the screening period and run-in period defined the run-in baseline and treatment baseline, respectively.
A primary responder had at least a 30% decrease in treatment baseline score relative to run-in baseline score. For these responders, efficacy failure required a sustained worsening pattern: 3 consecutive days, or 4 days in a row with one day missing and the other 3 days meeting the criteria. The qualifying daily evening pain score had to be at least 4 and show an increase of at least 30% relative to treatment baseline. Time was counted from Day 1 of double-blind treatment to the first documented failure, with a stated timeframe of up to 28 days.
Time-to-event endpoints are useful when both whether an event occurs and when it occurs are relevant. A median time describes the point by which half of the analysis population has experienced the event, under the analysis used. It is not a measure of average pain intensity and does not state how many participants met the responder definition in the full randomized population.
The endpoint is clinically interpretable as time until a specified worsening pattern, but it depends on repeated pain ratings and the registry’s precise event rule. The group medians and their 95% confidence intervals are not reported in the registry record, so the duration of response and the precision of any group comparison cannot be assessed from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies time to efficacy failure among primary responders as the primary outcome. It lists 37 participants in the MK-6096 endpoint group and 28 in the placebo endpoint group, but the median value, confidence interval limits, and spread are absent for both groups. The record also indicates that values were missing or not estimable for a two-arm comparison of this median-time endpoint. Consequently, the posted results do not support a numerical estimate of how the groups differed in time to efficacy failure.
This is not evidence that the groups had the same outcome. It means the registry record does not provide an estimable comparison for this endpoint. Without the group estimates or a reported treatment-effect estimate, the direction and size of a difference cannot be established from these entries. The uncertainty around any difference also cannot be characterized.
The endpoint is restricted to people who qualified as primary responders and continued into double-blind treatment. The comparison therefore concerns persistence of response within that selected analysis population. It does not answer how the treatments compare for all 170 enrolled participants, and the endpoint counts should not be treated as the number randomized to each group. The registry record does not report the number of randomized participants who became primary responders, the reasons others were not included, or a full flow accounting.
Time-to-event analyses may incorporate information about when events occur and, depending on the analysis, participants who have not experienced an event by the end of observation. Such analyses rely on clear event definitions and handling of incomplete follow-up. The registry record does not describe the censoring rules, the statistical model, or the handling of incomplete pain ratings for this outcome. It also does not report a hazard ratio in the registry record for this analysis. A hazard ratio should therefore not be inferred from the group counts or from the endpoint definition.
Other outcomes are listed, including all-responder time to efficacy failure and changes in pain-intensity scores for primary and all responders. The record lists 6 outcome measures and 3 secondary outcomes, but does not provide numerical results for them in the registry record. Their presence does not fill the gap in the primary endpoint estimate.
The practical statistical conclusion is limited: the registry describes a randomized comparison and a defined endpoint, but it does not supply an interpretable numerical primary result. Confidence intervals are also absent, so precision cannot be judged. Any sample-size illustrations are planning calculations based on stated assumptions, not observed power and not evidence that the trial detected or excluded an effect.
9. Statistical Methods Explained
General: A time-to-event outcome records the time from a defined starting point until a specified event. In this trial, the starting point was Day 1 of double-blind treatment, and the event was the first documented efficacy failure under the stated pain-rating rule. The endpoint is different from a single measurement of pain intensity because it incorporates the timing of a qualifying worsening pattern.
What does a median time mean?
General: The median time is the time by which half of the analysis population has experienced the event, as estimated under the chosen analysis. It is a summary of the event-time distribution, not a statement that every participant experienced the event at that time. A median alone also does not describe the full shape of the distribution. The registry record specifies median time and a 95% confidence interval as the intended summaries, but reports no median or interval limits for either group.
A confidence interval expresses uncertainty about an estimated quantity under the statistical method used. A narrower interval indicates greater precision than a wider interval, all else being comparable. Here, neither the group intervals nor a numerical comparison interval is reported in the registry record. Precision therefore cannot be evaluated. The absence of an interval is not itself evidence of a narrow or wide uncertainty range.
How is efficacy failure defined?
The event rule uses repeated evening pain scores. A qualifying pattern is 3 consecutive days, or 4 days in a row with one day missing and the other 3 days meeting the specified conditions. Each of those observed days must have a score of at least 4 and an increase of at least 30% relative to treatment baseline. The first documented occurrence defines the endpoint event time. This operational definition makes the endpoint reproducible in principle, but the record does not explain how other missing ratings, ties in timing, or deviations from the expected rating schedule were handled.
The responder definition is applied before the primary endpoint analysis. A participant had to show at least a 30% decrease in treatment baseline pain relative to run-in baseline pain to be classified as a primary responder. Conditioning the endpoint on that response status changes the population being described: the primary result is about time to failure among responders who continued, not response attainment among everyone enrolled. The registry record does not report the responder count among all randomized participants or the reasons for not entering the endpoint population.
What does a two-group comparison require?
General: A treatment comparison needs an effect estimate and a measure of its uncertainty to communicate both the apparent difference and how precisely it has been estimated. For a time-to-event outcome, possible summaries include group-specific event-time summaries or a model-based comparison. The choice depends on the prespecified analysis and the data. The record identifies the median as the group summary but does not provide the median values, confidence intervals, or a hazard ratio for this endpoint. It states that values were missing or not estimable for a two-arm comparison of the median-time outcome. No alternative comparison should be reconstructed from the group counts.
General: Time-to-event methods can account for participants whose event time is not observed during follow-up by using censoring rules. Those rules specify what information contributes when a participant has not had an event by the end of observed follow-up or when follow-up ends early. The registry record does not report the censoring method or the model used. The endpoint timeframe is listed as up to 28 days, while the arm descriptions state a 2-week double-blind period; the record does not clarify the relationship between these durations.
Why can over-dispersion matter?
General: Over-dispersion is a concern for count outcomes when the observed variation exceeds what a statistical model assumes. It can make uncertainty estimates too small if the model does not allow for that extra variation. It is not a specific reported issue for this trial’s primary endpoint, which is a time-to-event measure rather than a count outcome. The registry record does not describe an over-dispersion assessment, and none should be inferred from the endpoint entries.
What can planning calculations tell the reader?
General: Sample-size calculations can illustrate how many participants or events might be needed under specified assumptions to detect a target effect with a chosen error rate and power. Such calculations are prospective planning aids; they are not observed power, and they do not show whether a trial actually found a difference. The stated assumptions for the planning illustrations include a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. The record also specifies that time-to-event illustrations use total events, while other illustrations use participants per arm. These assumptions do not replace the trial’s own design rationale, which is not reported in the registry record.
Because the primary median estimates are absent, there is no reported observed effect from this endpoint to interpret alongside a planning illustration. No sample-size justification, interim analysis plan, statistical analysis plan, or method for adjusting estimates for other factors is reported in the registry record. The appropriate reading is therefore descriptive: the endpoint and analysis population are defined, but the principal numerical result and important analysis details are unavailable.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 6 outcome measures, 3 secondary outcomes, and 2 analyses. It does not report a multiplicity strategy, such as an adjustment to account for evaluating multiple outcomes or analyses. Without that information, the extent to which any reported significance assessment would control the chance of false-positive findings across several tests cannot be judged. No such assessment should be inferred from the number of listed outcomes alone.
The primary analysis population is described as randomized participants who continued into the double-blind period and met the primary-responder criteria. This is not the same as an analysis of every enrolled participant. The record does not report whether an intention-to-treat analysis was performed, how many participants were randomized in total, or how participants moved through the run-in and treatment periods.
The outcome depends on repeated pain ratings, but the registry record does not state how missing ratings were handled beyond the specific rule allowing one missing day in a qualifying 4-day sequence. It does not describe other missing-data procedures, withdrawals, censoring rules, or sensitivity analyses. Those omissions matter because incomplete follow-up can affect which event times are observed and how uncertainty is estimated.
The median-time values and confidence intervals are not reported, and the registry indicates that values were missing or not estimable for a two-arm comparison. Thus, the lack of a numerical result is separate from the lack of detail on multiplicity and missing-data methods: both limit assessment, but they are distinct limitations. The registry record does not report interim analyses or a full statistical analysis plan.
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 |
|---|---|---|---|
| MK-6096 10 mg - Run-in Period | 3 | 182 | 1.6% |
| MK-6096 10 Mg-Double Blind Period | 0 | 88 | 0.0% |
| Placebo- Double-Blind Period | 1 | 82 | 1.2% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| MK-6096 10 mg - Run-in Period | 0 of 182 |
| MK-6096 10 Mg-Double Blind Period | 0 of 88 |
| Placebo- Double-Blind Period | 0 of 82 |
Most frequent serious adverse event terms
| Event term | Organ system | MK-6096 10 mg - Run-in Period | MK-6096 10 Mg-Double Blind Period | Placebo- Double-Blind Period |
|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | 1 of 182 | 0 of 88 | 0 of 82 |
| Cardio-respiratory arrest | Cardiac disorders | 1 of 182 | 0 of 88 | 0 of 82 |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 182 | 0 of 88 | 0 of 82 |
| Sepsis syndrome | Infections and infestations | 1 of 182 | 0 of 88 | 0 of 82 |
| Encephalopathy | Nervous system disorders | 1 of 182 | 0 of 88 | 0 of 82 |
| Syncope | Nervous system disorders | 1 of 182 | 0 of 88 | 0 of 82 |
| Renal failure acute | Renal and urinary disorders | 1 of 182 | 0 of 88 | 0 of 82 |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | 1 of 182 | 0 of 88 | 0 of 82 |
| Blood pressure inadequately controlled | Vascular disorders | 1 of 182 | 0 of 88 | 0 of 82 |
| Chest pain | General disorders | 0 of 182 | 0 of 88 | 1 of 82 |
Serious events with the highest arm-level rate: chest pain (1.2%), acute myocardial infarction (0.5%), cardio-respiratory arrest (0.5%), upper gastrointestinal haemorrhage (0.5%), sepsis syndrome (0.5%).
The registry record reports serious adverse event counts for three periods or groups. During the MK-6096 10 mg run-in period, 3 of 182 participants at risk were reported as affected by a serious adverse event. During the double-blind MK-6096 10 mg period, 0 of 88 were affected; during the placebo double-blind period, 1 of 82 was affected. The recorded counts for other adverse events are 0 in all three entries.
These figures should be read as period-specific entries, not as a direct comparison of equal-sized groups across the full trial. The run-in entry lists 182 participants at risk, while the registry enrollment is 170; the record does not explain this difference. It also does not provide enough information to determine how participants may have contributed across periods. The figures should not be combined or converted into comparative rates.
The listed serious-event terms and percentages are chest pain, 1.2%; acute myocardial infarction, 0.5%; cardio-respiratory arrest, 0.5%; upper gastrointestinal haemorrhage, 0.5%; sepsis syndrome, 0.5%; and encephalopathy, 0.5%. The record does not specify in these entries how those terms map to the period-specific groups. Death counts are not reported in the registry record. These entries describe reported events; they do not establish a causal relationship to treatment or provide a complete assessment of safety.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, triple-masked, placebo-controlled, parallel-group phase IIa trial evaluated MK-6096 for painful diabetic neuropathy in adults. It defines a primary endpoint focused on time to a specified worsening pattern among primary responders who continued into double-blind treatment. It also gives the intended group summaries and some endpoint group counts.
What the record does not establish is the size or direction of the primary treatment difference. The median estimates and confidence intervals for both groups are absent, and a two-arm median-time comparison is identified as missing or not estimable. The record therefore cannot show whether time to efficacy failure was longer or shorter in either group, or how precise a difference might be. Missing estimates should not be interpreted as proof of no difference.
The endpoint does not represent pain outcomes for all enrolled participants. It is conditional on achieving the primary-responder threshold and continuing into double-blind treatment. It also uses a particular repeated-rating rule, so its meaning is tied to the specified pain scale, baseline definition, and criteria for failure. The record does not report the overall responder rate or complete participant flow.
Safety entries report serious adverse event counts during the run-in and double-blind periods, but the record does not explain the difference between the enrollment figure and the run-in denominator, nor does it provide a clear mapping of listed event terms to treatment groups. The death counts are not reported in the registry record. These safety entries should not be used to make a causal or comprehensive safety judgment.
In short, the record supplies a study design and endpoint definition but not the numerical primary outcome needed to quantify the comparison. It supports a description of what was intended to be measured, not a conclusion about the magnitude, precision, or clinical importance of a treatment effect.
13. Why This Trial Matters Statistically
This trial illustrates why an endpoint definition and a numerical result serve different purposes. A detailed rule for efficacy failure makes clear what event the investigators intended to count and when timing began. But a defined endpoint cannot, by itself, show the observed result. Without group estimates and uncertainty intervals, readers cannot assess either the apparent difference or its precision.
It also highlights the importance of analysis populations. The primary outcome concerns participants who met a response threshold after the run-in and continued into double-blind treatment. That is a narrower question than the overall effect among everyone enrolled. Clear reporting of the number entering each analysis population and the reasons for exclusions is essential to understand who the result describes. Such participant-flow information is not reported in the registry record.
The period-specific safety denominators raise a separate reporting issue: they do not align with the enrollment figure, and the registry record does not explain the relationship. Denominators, timing, and analysis populations are central to interpreting event counts; counts without clear context are difficult to compare.
For biostatisticians and clinical researchers, the record is a reminder that reporting completeness affects what can be learned from a trial. A randomized design and a prespecified-looking endpoint description are useful, but the unavailable primary estimates and analysis details prevent a quantitative interpretation. Statistical transparency requires both a clearly described estimand and enough reported information to evaluate its estimate, uncertainty, and population.
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 primary limitation is that the registry record does not report either group’s median time to efficacy failure or its 95% confidence interval. It also identifies the two-arm median-time comparison as missing or not estimable. The principal treatment comparison therefore cannot be quantified or assessed for precision.
The analysis population is restricted to primary responders who continued into double-blind treatment. The record does not report the number of randomized participants who met this definition, the number who continued, or the reasons for not contributing to the primary endpoint. The endpoint group counts are 37 for MK-6096 and 28 for placebo, but do not substitute for a participant-flow account.
The outcome timeframe is described as up to 28 days, while the double-blind arm descriptions specify 2 weeks of treatment. The registry record does not reconcile these timeframes. It also does not report the time-to-event model, censoring rules, handling of missing pain ratings beyond the event definition’s allowance, or sensitivity analyses. Multiplicity procedures, interim analyses, the full statistical analysis plan, and the trial’s sample-size justification are not reported in the registry record.
Safety interpretation is limited by the difference between the enrollment figure of 170 and the run-in at-risk count of 182. The record does not explain this discrepancy or clarify how the serious-event terms and percentages relate to the listed treatment periods. Death counts are not reported in the registry record. These limitations restrict interpretation of both the efficacy comparison and the safety entries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate MK-6096 in the Treatment of Painful Diabetic Neuropathy (PDN) in Adults (MK-6096-021) — NCT01564459.
- Registry record last updated 2018-11-07; status last verified 2018-10.
- Results first posted 2016-08-10.
- 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.
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18. Record Summary
This completed phase IIa randomized, triple-masked, parallel-group trial evaluated MK-6096 against placebo in adults with painful diabetic neuropathy. Registry enrollment was 170. Both groups received MK-6096 10 mg once daily during a 1-week run-in; during the 2-week double-blind period, one group continued MK-6096 and the other received placebo.
The primary endpoint was time to efficacy failure among primary responders who continued into double-blind treatment. The registry lists 37 participants in the MK-6096 endpoint group and 28 in the placebo group, but does not report median estimates or confidence intervals and states that a two-arm median-time comparison was missing or not estimable. Secondary outcomes include all-responder time to efficacy failure and pain-intensity changes.
Serious adverse event counts are reported by period, but the relationship between the period denominators and enrollment is not explained. The registry record does not report the primary numerical result, detailed missing-data or censoring methods, or a complete participant-flow account.