A Study of the Safety and Efficacy of MK-6096 for Migraine Prophylaxis in Participants With Episodic Migraine (MK-6096-020): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Safety and Efficacy of MK-6096 for Migraine Prophylaxis in Participants With Episodic Migraine (MK-6096-020) (NCT01513291), a randomized phase 2 study. The primary outcome is Mean Change From Baseline in Monthly Migraine Days.

2. Clinical Question

The clinical question is about prevention over the trial’s Treatment Period, rather than treatment of an individual migraine episode. Participants recorded headache diary data during Screening and Treatment. A migraine was defined in the registry as a headache with at least one associated symptom of aura, photophobia, phonophobia, nausea, or vomiting. This operational definition determines which diary entries contribute to the migraine-day measure. The primary endpoint asks whether the average monthly frequency changed from baseline, and whether the change differed between the randomized treatment groups. The available registry description establishes the question and endpoint but does not report the estimated changes, their uncertainty, or a test of the between-group contrast.

3. Trial Design

The registry identifies this as a Phase IIa, multicenter, randomized, placebo-controlled trial with parallel groups. It records triple masking, while the arm descriptions characterize treatment as double-blind. The record does not explain the distinction between those masking descriptions. The listed enrollment is 237, and the status is completed. The registry gives a start date of 2012-02-06 and a primary completion date of 2012-10-03.

After the 28-day Screening period, participants were randomized to MK-6096 or placebo for a 12-week Treatment Period. The MK-6096 regimen was two 5 mg tablets, taken orally once daily, and the placebo regimen was two tablets taken orally once daily. The primary endpoint applied to the Treatment Period. Participants who completed that period received study drug or placebo during an additional 2-week Run-out Period. Assignment for the Run-out Period was determined at initial randomization, with participants originally assigned placebo continuing placebo. Participants originally assigned MK-6096 were assigned MK-6096 or placebo in a 1:1 ratio for Run-out.

The Treatment Period and Run-out Period answer different descriptive questions. The primary efficacy outcome is specified for baseline and the average over Weeks 0-12; the record does not identify it as a Run-out analysis. The safety listings distinguish Treatment Period groups from Run-out treatment sequences. Those periods and groups should therefore not be treated as interchangeable when interpreting the listed counts.

The registry lists six outcome measures and six analyses, but the available description does not give the complete analysis plan, allocation concealment procedures, or the rationale for the planned enrollment. Those details are not reported in the registry record. A completed status indicates that the study is recorded as completed; it does not supply the missing numerical efficacy results or explain how every randomized participant contributed to each analysis.

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.

Before assignment: A total of 423 participants were screened. Of these, 237 participants completed screening and met the eligibility criteria, including the required number of migraine days during the Screening period.

Treatment Period

Reasons for not completing this period:

Run-out Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The population analyzed included participants who received at least one dose of double-blind study treatment and had at least one evaluable endpoint measurement, including those with only a baseline measurement. This outcome measure applied only to the Treatment Period and was not analyzed for the Run-out Period.

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.

Population: Baseline characteristics are reported for all randomized participants

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in Monthly Migraine Days, measured over Baseline and average over Treatment Period (Weeks 0-12).

The primary endpoint is the mean change from baseline in monthly migraine days, expressed in days per month. Baseline was assessed during Screening, and the follow-up value was averaged over the 12-week Treatment Period. The endpoint description says participants recorded information in an electronic migraine headache diary in the evening, approximately one hour before bed and before taking study medication. A migraine was defined as a headache with at least one associated symptom of aura, photophobia, phonophobia, nausea, or vomiting.

A change score expresses how the measured monthly migraine-day frequency during treatment differs from the participant’s baseline frequency. The registry specifies that a negative number indicates a reduction in mean monthly migraine days. The planned group summary is a least-squares mean, with standard error identified as the dispersion measure. These summaries can account for the analysis model’s structure, but the registry does not report the model specification or numerical estimates.

Diary-based frequency is relevant to the stated prevention question because it measures the occurrence of migraine days across the treatment period rather than relying on a single observation. Averaging over the Treatment Period represents frequency across that period. However, the registry record does not provide the observed endpoint values, the estimated difference between groups, a confidence interval, or a p-value. The direction and precision of the primary comparison therefore cannot be assessed from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a continuous measure: mean change from baseline in monthly migraine days. For a continuous measure, an analysis commonly summarizes the distribution of observed values and estimates a group mean or model-based mean. Here, the specified parameter is a least-squares mean. In general, a least-squares mean is an estimate from a statistical model rather than necessarily the raw arithmetic average. Its meaning depends on the model terms, assumptions, and analysis population. The model specification is not reported in the registry record, so the adjustments and exact interpretation of that estimate cannot be established.

What does a change score represent?

A change score compares a follow-up measurement with a baseline measurement. For this endpoint, negative values indicate a reduction in mean monthly migraine days, as stated in the registry description. The treatment question is not answered by looking only at whether either group changed from baseline. The randomized comparison is the difference between the groups’ changes, interpreted alongside its uncertainty. A within-group change can reflect treatment, time, measurement variation, or other influences; the placebo group provides a concurrent comparison for the treatment period. The registry does not report the group estimates or the between-group contrast.

How should standard error and confidence intervals be understood?

Standard error describes the estimated variability of an estimate across repeated samples under the analysis assumptions. Smaller standard errors generally indicate more precise estimates, while larger standard errors indicate less precision. A standard error is not the same thing as the spread of individual participant measurements. A confidence interval uses an estimate and its uncertainty to express a range of values compatible with the data and model at a stated confidence level. The record identifies standard error as the dispersion measure for the primary least-squares mean but gives no values and no confidence interval for the comparison. Precision therefore cannot be evaluated from the available endpoint description.

Why is the randomized contrast central?

Random allocation is intended to make treatment groups comparable at the point of assignment, on average, with respect to factors that could affect outcomes. In a parallel-group trial, participants remain assigned to their original treatment group for the primary comparison. The relevant inference is therefore about the difference between randomized groups, under the chosen analysis approach. Randomization does not by itself prevent missing diary data, ensure adherence, or determine how participants with incomplete measurements are handled. The registry record does not report those details.

What does the planning illustration mean?

The planning assumptions describe an illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Such calculations describe how a hypothetical future study might be sized under those assumptions; they are not observed power for this trial and do not show that the trial was designed using the same effect or assumptions. Sample-size illustrations are planning tools, not results of the randomized comparison. The registry record does not report the trial’s own sample-size justification.

Why can over-dispersion matter?

As a general statistical point, over-dispersion occurs when observed variability is greater than a model assumes. If the model understates variability, standard errors can be too small and uncertainty can appear narrower than warranted. If variability is modeled appropriately, the resulting uncertainty better reflects the data structure. This trial’s primary outcome is summarized as a continuous measure, and the record does not describe an over-dispersion assessment or identify a count model for the primary analysis. The concept is therefore general rather than a claim about a feature detected in this trial.

How do secondary outcomes affect inference?

The registry lists six outcome measures and six analyses, including outcomes based on headache days and on the proportion of participants with specified reductions in monthly migraine days. Examining multiple outcomes or analyses can create a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase. Statistical methods may address this through a prespecified testing hierarchy or adjustment, but the analysis plan and any multiplicity procedure are not reported in the registry record. No claim can be made about whether adjustment was used.

Finally, statistical significance and clinical importance are different ideas. A p-value, when available, concerns the compatibility of the data with a statistical null hypothesis under specified assumptions; it does not state the probability that a treatment works. The size and precision of the estimated contrast are also needed for interpretation. Neither the primary p-value nor the numerical contrast is reported, so the statistical evidence and practical magnitude cannot be assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and six analyses. The primary outcome is mean change from baseline in monthly migraine days. Secondary outcomes include mean change in monthly headache days and the percentages of participants with at least a 50% or at least a 30% reduction from baseline in monthly migraine days. The available information does not give the complete set of outcome definitions, identify a formal testing hierarchy, or describe any adjustment for multiple comparisons. Whether multiplicity was addressed is not reported in the registry record.

Multiplicity matters because examining several outcomes or analyses creates several opportunities to observe an apparently unusual result. A prespecified strategy can help define which comparisons carry confirmatory weight and how evidence across them should be interpreted. Without the statistical plan and results, it is not possible to determine whether the listed analyses were confirmatory, exploratory, adjusted, or interpreted under another approach.

The primary analysis population is described as participants who received at least one dose of double-blind study treatment and had at least one evaluable endpoint measurement, including those with only a baseline measurement. This is not described as all randomized participants. The record does not report the number included in the primary analysis, the number with missing diary data, or how missing measurements were handled. The endpoint population description also says the outcome applied only to the Treatment Period; further detail about its applicability is not reported in the registry record.

Missing-data methods can affect estimates when observations are incomplete, particularly if the chance of missingness relates to participants’ health, treatment, or outcome. General approaches include modeling available measurements or making assumptions about unobserved values, but no particular approach should be attributed to this trial without documentation. The handling of protocol deviations, treatment discontinuation, and sensitivity analyses is not reported in the registry record. As a result, the robustness of the primary estimate to missing data and analysis choices cannot be assessed.

11. 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 lists serious adverse events and other adverse events separately for the Treatment Period and Run-out Period groups. During the Treatment Period, the MK-6096 group lists 120 participants at risk and 0 affected by serious adverse events; the placebo group lists 115 at risk and 0 affected. For other adverse events, the corresponding affected counts are 26 and 10.

For Run-out, the MK-6096 / MK-6096 group lists 50 participants at risk, with 0 affected by serious adverse events and 1 affected by other adverse events. The MK-6096 / placebo group lists 47 at risk, with 0 affected by serious adverse events and 4 affected by other adverse events. The placebo / placebo group lists 101 at risk, with 0 affected by serious adverse events and 1 affected by other adverse events. These entries are period- and treatment-sequence-specific and should not be combined across groups.

Zero listed serious adverse events means that the registry reports no affected participants in those particular entries; it does not establish that every possible safety outcome was absent. Counts of other adverse events are descriptive and do not by themselves establish a causal relationship to treatment. The registry does not provide event-level descriptions here, and death counts are not reported in the registry record.

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

The trial’s stated purpose was to evaluate the safety and efficacy of MK-6096 compared with placebo for migraine prevention in participants with episodic migraine. The registry specifies randomization, the Treatment Period, the primary endpoint, and the direction of change that represents a reduction in monthly migraine days. Those details define the intended comparison, but they do not report its result.

The available record does not state the least-squares mean changes in either group or the estimated treatment contrast. It also does not report a confidence interval or p-value for the primary endpoint. Accordingly, the evidence described in this record cannot determine whether the groups differed, how large any difference was, or how precisely it was estimated. The stated hypothesis should not be mistaken for a finding: it identifies what the trial set out to test.

Even when numerical results are available, statistical evidence is not identical to clinical importance. A small estimated difference can be statistically precise, while an uncertain estimate can be compatible with a range of effects. Interpreting importance would require the treatment-effect estimate and its uncertainty, as well as context for the outcome. Those numerical results and context are not reported in the registry record.

The safety counts offer a separate, limited description. No serious adverse events are listed in the reported groups, and other adverse-event counts are provided by period and treatment sequence. These figures do not establish that treatment is safe or unsafe overall, nor do they show causation. They are registry counts for the listed groups, without the broader detail needed to characterize each event. Death counts are not reported in the registry record.

The record therefore supports statements about what was planned and how selected results were tabulated, but not a conclusion about efficacy or an overall benefit-risk judgment. The absence of the primary numerical comparison in the available record is a substantial interpretive limitation. It should not be replaced by inference from the design, the study’s completed status, or the existence of secondary outcomes.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a clinical question is translated into a measurable endpoint and randomized comparison. The question concerns prevention in episodic migraine, and the primary measure is change in monthly migraine days from baseline over the 12-week Treatment Period. The registry also defines migraine using diary-recorded headache and associated symptoms. Clear endpoint definitions matter because they determine what is counted and which time period contributes to the analysis.

The randomized, placebo-controlled, parallel-group design provides a framework for comparing outcomes under the assigned treatment strategies. The stated least-squares mean and standard error indicate a model-based summary and an uncertainty measure, though the model details and estimates are not reported. This highlights why an endpoint name alone is insufficient for statistical interpretation: the numerical contrast, its precision, the analysis population, and the handling of incomplete data are also needed.

The record further illustrates the importance of separating efficacy outcomes from safety summaries and distinguishing the Treatment Period from Run-out. Safety entries are listed for treatment sequences and should be interpreted within those periods. The record’s secondary outcomes raise questions about multiplicity, but it does not report whether a testing strategy was applied. Without those methods and the results, readers cannot determine the evidential status of individual comparisons.

Most importantly, a completed randomized trial and a stated superiority hypothesis do not constitute an efficacy result. The primary comparison is not numerically reported in the available record. Recognizing that boundary is part of sound statistical reading: design information can explain what the analysis was meant to answer, while only reported estimates and uncertainty can show what the data support.

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 principal limitation for interpreting this trial record is that numerical results for the primary endpoint are not reported. The registry describes the endpoint and analysis population but gives no least-squares mean changes, between-group estimate, confidence interval, or p-value. The direction and magnitude of the primary comparison, and its precision, therefore cannot be evaluated.

The available description also does not report the model specification behind the least-squares means, the complete statistical analysis plan, or the handling of missing diary measurements. Although the analysis population is described, the number analyzed and the extent of missing outcome data are not reported in the registry record. No sensitivity analyses or details about protocol deviations are given. These omissions limit assessment of whether analysis choices could affect the result.

The registry lists secondary outcomes and analyses but does not describe a multiplicity strategy. It is therefore unclear how evidence across the multiple outcomes was intended to be interpreted. The record also does not explain the difference between its triple-masking classification and the arm descriptions’ use of double-blind. This discrepancy should not be resolved by assumption.

Safety information is limited to counts by listed period and group. Serious adverse events are reported as zero in the entries, while other adverse-event counts are provided; event details and death counts are not reported in the registry record. These summaries do not provide a full account of event severity, timing, or causal attribution. Finally, the stated enrollment and at-risk counts are recorded for different purposes, and the registry description does not explain their relationship. The available information does not support inferring unreported participant-flow details.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of the Safety and Efficacy of MK-6096 for Migraine Prophylaxis in Participants With Episodic Migraine (MK-6096-020) — NCT01513291.
• Registry record last updated 2018-11-07; status last verified 2018-10.
• Results first posted 2016-07-20.
• 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.

18. Record Summary

The registry record describes NCT01513291, a completed Phase IIa, multicenter, randomized, placebo-controlled parallel-group trial of MK-6096 for migraine prophylaxis in participants with episodic migraine. Listed enrollment is 237. Participants were assigned to MK-6096 10 mg once daily or placebo during a 12-week Treatment Period following a 28-day Screening period. A 2-week Run-out Period followed for participants who completed treatment.

The primary endpoint was mean change from baseline in monthly migraine days, with a least-squares mean and standard error specified. The registry states that negative change indicates a reduction. Numerical primary efficacy results and the statistical comparison are not reported in the available record. Safety listings report zero serious adverse events in each listed group and provide separate other adverse-event counts. Death counts, detailed missing-data methods, and the multiplicity strategy are not reported in the registry record.