A Pharmacokinetic Study of MK-1602 in the Treatment of Acute Migraine (MK-1602-007): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pharmacokinetic Study of MK-1602 in the Treatment of Acute Migraine (MK-1602-007) (NCT01657370), a randomized phase 2 study. The primary outcome is Dry Blood Spot (DBS) MK-1602 Concentration at 2 Hours Post-Dose on Migraine Treatment Day.

2. Clinical Question

3. Trial Design

This was a Phase IIb, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of MK-1602 in acute migraine. The registry record lists an enrollment of 195 and a completed status. The recorded study start is 2012-08, and primary completion is recorded as 2012-11. The sponsor is Allergan.

Participants were assigned to placebo or one of five MK-1602 dose groups: 1 mg, 10 mg, 25 mg, 50 mg, or 100 mg. Each group’s regimen involved three oral doses: the first at onset of a moderate or severe migraine on Day 1, the second in the evening of Day 3, and the third on Day 4. Participants could take rescue medication after 2 hours if necessary. The registry record does not report the randomization sequence, allocation ratio, concealment procedures, or the details of how blinding was maintained.

The stated purpose was to characterize MK-1602 pharmacokinetics, including possible influences of demographic and other variables, and to evaluate the relationship between drug concentrations and efficacy. The posted primary outcome is the geometric mean dried blood spot concentration at 2 hours after dose 1, for participants in the pharmacokinetic analysis population who received treatment and had analyzable data. The record also lists symptom outcomes at 2 hours and sustained outcomes over a later period.

The registry record does not report the planned sample-size justification, a detailed statistical analysis plan, or interim analyses. It also does not describe the participant flow by randomized group or give fuller baseline characteristics. Thus, the design can be described from the recorded randomization, masking, parallel-group structure, dose groups, and scheduled treatment, but not from unreported operational details.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants from the Pharmacokinetic Analysis Population, all participant who received treatment, with data available for 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.

Population: All Subjects as Treated Population included all randomized participants who received at least 1 dose of study treatment.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Dry Blood Spot (DBS) MK-1602 Concentration at 2 Hours Post-Dose on Migraine Treatment Day, measured over 2 hours post dose 1.

The primary endpoint is the dried blood spot concentration of MK-1602, measured in nanomolar (nM) units 2 hours after the first dose on the migraine treatment day. Participants collected blood by fingerstick onto a card; the card was sent to a laboratory, where concentration was determined using a dried blood spot assay. The endpoint is summarized as a geometric mean, with a geometric coefficient of variation describing spread.

Concentration is a pharmacokinetic measure: it describes the amount of drug measured in the sampled blood at a specified time after dosing. It is useful for characterizing drug exposure and for comparing the recorded concentrations across dose groups. It is not itself a direct measure of symptom improvement. The study description also names an interest in relating concentrations to efficacy, but results from such a relationship analysis are not reported in the registry record.

The posted geometric means are 1.9 nM for MK-1602 1 mg, 17.0 nM for 10 mg, 43.8 nM for 25 mg, 52.7 nM for 50 mg, and 184.8 nM for 100 mg. The corresponding geometric coefficients of variation are 73.0, 74.0, 130.0, 270.0, and 170.0. The numbers of participants with reported concentration data are 21, 23, 27, 22, and 23, respectively. Confidence intervals for these primary estimates are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary summary uses a geometric mean rather than an arithmetic mean. General statistical explanation: concentration measurements are often positive and may be unevenly distributed, with some observations farther from the center than others. A geometric mean is based on the logarithms of the measurements and then returned to the original measurement scale. It summarizes a multiplicative center, which can be useful when values vary proportionally rather than by a fixed additive amount. The registry record identifies the primary statistic as a geometric mean, but does not report whether concentrations were log-transformed for additional modeling or how values below assay limits, if any, were handled.

What does the geometric coefficient of variation describe?

The geometric coefficient of variation is a measure of relative variability around a geometric mean. General statistical explanation: it helps describe how dispersed measurements are in relation to the central concentration, rather than expressing spread in the concentration’s original units. A high value indicates that measurements are widely dispersed relative to the group’s scale. The posted coefficients vary across dose groups, with the largest reported value in the 50 mg group. Because the registry record does not give a distribution plot or individual measurements, the coefficient should be read as a summary rather than a complete account of the data shape.

Why is there no primary confidence interval or comparison?

The registry record posts concentration means and geometric coefficients of variation by dose group, but no confidence intervals, p-values, or formal arm-to-arm comparisons for this primary outcome. General statistical explanation: a confidence interval describes the range of values reasonably compatible with an estimate under a specified method and assumptions. Without a posted interval or an inferential model, the precision of each geometric mean and the uncertainty around differences between groups cannot be evaluated from the registry results. A visual rise in reported means across the dose groups is descriptive and should not be mistaken for a statistical test.

How should the symptom outcomes be read?

The three secondary outcomes with detailed results are binary summaries: the percentage reporting absence of phonophobia, absence of photophobia, and absence of nausea at 2 hours after dose 1. For these outcomes, the registry record gives group percentages and 95% confidence intervals. Some unadjusted comparisons against placebo are also posted as risk differences with confidence intervals and p-values. General statistical explanation: a risk difference expresses the difference between the event proportions in two groups; a confidence interval covering zero is compatible with no difference under that interval method. These are unadjusted comparisons, meaning the record does not report adjustment for other variables in those comparisons.

The listed symptom outcome estimates are based on relatively small group counts, and their confidence intervals are broad. General statistical explanation: when event counts and group sizes are limited, estimates can be imprecise; the interval conveys that uncertainty rather than proving that the true group difference is zero. The posted p-values are unadjusted and there are multiple secondary outcomes and dose comparisons. The registry record does not report a multiplicity adjustment, so these nominal results should not be treated as if they were protected against the increased chance of chance findings that can arise from examining many comparisons.

What do the planning illustrations mean?

Some secondary comparisons include planning illustrations for hypothetical future studies. They describe participants per arm for 80% power and participants per arm for 90% power, under the stated assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Rows represent planning for 100%, 75%, or 50% of the observed effect. General statistical explanation: power is the probability that a planned analysis will detect an effect of a specified size under its assumptions. These figures are not observed power for this completed study; they are sample-size planning illustrations based on the observed comparison and assumptions. They do not establish what sample size the original trial was designed to use. The trial’s own sample-size justification is not reported in the registry record.

The registry record lists no reported analyses for the secondary outcomes. The posted unadjusted comparison statistics are therefore not evidence of a sponsor-reported adjusted analysis. No detailed model specification, covariate plan, or approach to missing secondary data is reported. For binary outcomes, the record gives denominators and percentages, but does not explain how missing responses were treated. These omissions limit how fully the analysis can be reproduced or evaluated.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes, including symptom outcomes at 2 hours and sustained or total migraine outcomes over later periods. It also includes comparisons of several MK-1602 doses with placebo for the detailed secondary results. No multiplicity adjustment, hierarchical testing sequence, or other strategy for controlling the overall false-positive risk is reported in the registry record. Consequently, the posted unadjusted p-values should be interpreted cautiously and not as though they came from a single pre-specified confirmatory test.

General statistical explanation: multiplicity matters when many hypotheses are examined because an isolated small p-value can occur by chance even when no underlying difference exists. Adjustment methods or a preplanned testing order can address this issue, but the registry record does not identify any such method. The record also lists no reported analyses for the secondary outcomes, so the posted comparisons do not establish that an analysis plan was carried out as written or that results were selected according to a stated testing hierarchy.

The primary outcome is reported for participants in the pharmacokinetic analysis population who received treatment and had data available for analysis. That definition indicates that the concentration summary is based on available data in treated participants, rather than all enrolled participants. The registry record does not report the number of missing concentration measurements, reasons for missing data, imputation methods, or sensitivity analyses. For secondary outcomes, missing-data handling is also not reported.

The registry record does not report a detailed analysis population definition for each symptom outcome, a full participant flow, or how participants who used rescue medication were handled in efficacy analyses. It does not report interim analyses, a full statistical analysis plan, or the sample-size justification for the original trial. These gaps prevent a complete assessment of pre-specification, missing-data assumptions, and the confirmatory status of the secondary comparisons.

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 adverse-event record reports zero participants with a serious adverse event in each listed group: placebo, MK-1602 1 mg, 10 mg, 25 mg, 50 mg, and 100 mg. The numbers at risk for the serious-event summaries are 28, 28, 26, 28, 28, and 27, respectively. These are the posted counts for the recorded groups; they should not be interpreted as proof that serious events cannot occur or that risks are equivalent.

Other adverse events affected 6 participants in placebo, 6 in MK-1602 1 mg, 2 in 10 mg, 10 in 25 mg, 7 in 50 mg, and 7 in 100 mg. The corresponding numbers at risk are 28, 28, 26, 28, 28, and 27. The registry record does not provide detailed event terms in the posted serious-event list, which is empty. Death counts are not reported in the registry record.

These figures are descriptive counts from the registry record. They do not provide a formal comparison of safety between groups, and the record does not state a statistical method for such a comparison. The short recorded study period and available group counts also limit what can be inferred about uncommon or later events.

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

The primary result means that the registry record reports measured MK-1602 concentrations in dried blood spots 2 hours after the first dose for five dose groups. The reported geometric means rise overall across the listed dose levels, with substantial variation within groups. These findings provide a pharmacokinetic description at one specified sampling time. They do not, by themselves, show whether participants experienced symptom improvement or whether concentration predicts efficacy.

The secondary symptom results describe the percentages recorded for several 2-hour outcomes, with uncertainty intervals for the group estimates and unadjusted comparisons for some dose groups. Those findings are exploratory in light of the multiple outcomes and comparisons and the absence of a reported multiplicity procedure. The registry record does not report the results for all listed secondary outcomes, nor does it report a formal analysis connecting concentration with efficacy.

General statistical explanation: an estimate is not the same as certainty about the underlying effect. Confidence intervals communicate uncertainty under a statistical method, while a p-value assesses compatibility with a specified null hypothesis under its assumptions. Neither statistic proves that a treatment is beneficial or ineffective. In this record, the primary concentration outcome has no posted confidence intervals or inferential comparisons, and the secondary comparisons are unadjusted.

The record also reports adverse-event counts, including no serious adverse events in the listed groups, but these counts are not a comprehensive guarantee about safety. They reflect the recorded participants and observation period. Overall, the posted data support a description of concentration measurements and selected symptom and adverse-event counts, not a definitive claim about clinical efficacy, a concentration-efficacy mechanism, or comparative safety.

13. Why This Trial Matters Statistically

This trial is statistically informative because it distinguishes a pharmacokinetic endpoint from clinical symptom outcomes. The primary measure is drug concentration at a fixed time after dose 1, while the secondary measures concern migraine symptoms and their persistence. Keeping these questions separate is important: concentration summaries describe exposure, but do not automatically establish a clinical effect.

The group summaries also illustrate why variability matters. The geometric means differ across dose groups, while the geometric coefficients of variation indicate substantial spread around those group summaries. A mean alone can obscure that variation. Without confidence intervals or a formal comparison for the primary endpoint, readers can describe the pattern but cannot determine the inferential precision of differences between dose groups from the registry results.

The record further illustrates the limits of interpreting many secondary comparisons. Several outcomes and dose groups are relevant, but no multiplicity procedure is reported. Unadjusted p-values and confidence intervals can be useful descriptive evidence, yet they do not have the same confirmatory force as a pre-specified analysis with a documented strategy for multiple testing. Planning illustrations based on observed effects also need careful interpretation: they describe hypothetical future sample sizes under stated assumptions and are not observed power for this study.

Finally, reporting gaps matter to reproducibility. The registry record does not provide a detailed analysis plan, missing-data procedures, or a sample-size justification. Recognizing those absences is part of statistical interpretation, not a reason to speculate about what the investigators may have done. The posted summaries remain useful for understanding the measured outcomes while defining the limits of what can be concluded.

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 pharmacokinetic outcome is reported only as a geometric mean and geometric coefficient of variation for each dose group. Confidence intervals, formal comparisons, and a dose-response model are not reported in the registry record. The group pattern can therefore be described, but the precision of the means and uncertainty around between-dose differences cannot be assessed using the posted primary results.

The concentration analysis includes treated participants with data available for analysis. The record does not report how many participants lacked usable concentration measurements, why data were unavailable, or whether missingness differed by group. It also does not report assay performance details, handling of measurements outside assay limits, or distributions of individual concentrations.

Although the study purpose includes assessing demographic and other influences on pharmacokinetics and the relationship between concentration and efficacy, results for those analyses are not reported in the registry record. Numerical results are also not reported for four of the seven listed secondary outcomes. This limits evaluation of the study’s broader stated aims.

The secondary comparisons are unadjusted, and no approach to multiplicity is reported. The record does not describe how rescue medication use was incorporated into analyses, how missing symptom responses were handled, or whether outcomes were analyzed according to a defined population beyond the primary population description. Baseline characteristics and participant flow are not reported in the available record.

Lastly, the recorded enrollment and the numbers contributing to specific outcomes are not accompanied by the original sample-size justification or a detailed analysis plan. The planning illustrations attached to some comparisons are based on observed effects and assumptions for hypothetical studies; they do not establish the rationale or operating characteristics of the completed trial.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Pharmacokinetic Study of MK-1602 in the Treatment of Acute Migraine (MK-1602-007) — NCT01657370.
• Registry record last updated 2016-12-09; status last verified 2016-10.
• Results first posted 2016-12-09.
• 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

NCT01657370 is a completed Phase IIb, multicenter, randomized, double-blind, placebo-controlled, parallel-group study sponsored by Allergan. The registry record lists an enrollment of 195, a start date of 2012-08, and primary completion in 2012-11. Participants received placebo or oral MK-1602 at 1 mg, 10 mg, 25 mg, 50 mg, or 100 mg, with three scheduled doses and rescue medication available after 2 hours if necessary.

The primary outcome is the geometric mean MK-1602 concentration in dried blood spots 2 hours after dose 1. Posted group means rise overall across the dose groups, alongside substantial geometric coefficients of variation. The record also posts detailed results for three 2-hour symptom outcomes and adverse-event counts. Formal primary comparisons, multiplicity procedures, detailed missing-data methods, and results for several listed secondary outcomes are not reported in the registry record. The posted summaries support descriptive interpretation, with limits on conclusions about efficacy, concentration-efficacy relationships, and comparative safety.