Treatment of Multiple Attacks of Acute Migraine (0462-025): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Multiple Attacks of Acute Migraine (0462-025) (NCT00899379), a randomized phase 3 study. The primary outcome is Pain Relief at 2 Hours During the First Migraine Attack Period.

2. Clinical Question

The study was intended to evaluate treatment of multiple attacks rather than describe a single isolated attack. Its listed sequences vary whether placebo or rizatriptan was assigned during each attack period. The registry record does not provide enough information to determine how treatment effects across periods were estimated, how period or sequence effects were handled, or whether the primary comparison was adjusted for other factors.

The primary outcome is expressed as a number of participants meeting the stated pain-relief definition. Although the registry record identifies that endpoint and its analysis population, it does not give the group counts or an effect estimate for the first attack period. Consequently, the posted record cannot answer whether, or by how much, the observed pain-relief counts differed between treatment conditions. The safety counts are separate from this efficacy question and cannot fill that gap.

3. Trial Design

The registry record describes NCT00899379, titled “Treatment of Multiple Attacks of Acute Migraine (0462-025).” It identifies the study as phase 3, randomized, and parallel-group, with 473 enrolled. The official title describes an outpatient study of MK462 10 mg by mouth for multiple migraine attacks and calls it triple-blind; the registry’s masking entry says double. The record does not explain this difference or identify which people were masked.

The active intervention is listed as rizatriptan benzoate, and the comparator is placebo. Five treatment sequences are described. One assigns placebo in the first listed attack period and rizatriptan in the remaining periods; three place placebo in the second, third, or fourth period, respectively; and one lists rizatriptan in all four periods. These sequences indicate that the treatment allocation varied across attack periods. The record does not explain the sequence-allocation procedure, the length or spacing of periods, or how observations across periods were incorporated into the primary analysis.

The primary endpoint concerns pain relief at 2 hours during the first migraine attack period. Secondary outcomes are pain relief at 2 hours during the second, third, and fourth periods. The record therefore identifies outcomes across multiple attack periods, but it does not post results for them or a single treatment-effect estimate for the primary outcome.

The listed study start is 1995-04, and primary completion is 1996-01; status is completed. Organon and Co is identified as sponsor. The record does not report the detailed statistical analysis plan, the planned sample-size justification, or how participants were assigned among the five sequences. Those omissions limit reconstruction of the design and analysis from the registry entry alone.

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: Patients screened at a pretreatment visit were given allocated drug supply with instructions. If by 2 months after screening, a patient still had not treated a migraine attack with test medication, he/she was to be discontinued from the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The primary efficacy analysis used an all-patients-treated approach which included all patients who had at least one record of an efficacy measure after the initial dose. Missing values were imputed by carrying forward the preceding values in the same phase.

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.

6. Primary Endpoint

The registry lists the primary outcome as Pain Relief at 2 Hours During the First Migraine Attack Period, measured over 2 hours.

The primary endpoint counts participants who reported pain relief at 2 hours during the first migraine attack period. The record defines relief as a reduction in headache severity from grade 2 or 3 at baseline—moderate or severe—to grade 0 or 1 at 2 hours—no headache or mild headache. This is a binary outcome at the participant level: a person either meets the stated threshold or does not.

A threshold-based outcome can make a symptom measure easier to interpret than a change in a numerical score alone. It identifies a specific transition in headache severity that the study classified as relief. At the same time, the definition does not describe every possible symptom experience: for example, the registry record does not report other symptom measures, how relief was assessed beyond the stated grades, or whether participants also needed to meet another condition.

The endpoint is specific to the first attack period and the 2-hour assessment. The other listed efficacy outcomes use the same 2-hour timing for later attack periods. They should not be treated as interchangeable observations without knowing how the analysis accounted for treatment sequence and repeated attack periods.

The primary analysis population included participants who had at least one efficacy measure recorded after the initial dose. Missing values were imputed by carrying forward preceding values in the same phase. The registry record does not provide the number meeting the relief definition in either treatment condition, a treatment contrast, or an uncertainty interval. The endpoint definition can therefore be explained, but its comparative result cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

In general, randomization uses an allocation process intended to make treatment assignment independent of participants’ characteristics, rather than allowing treatment choice to depend on those characteristics. This can reduce systematic differences between groups at the start of a study. It does not guarantee that every relevant characteristic is balanced, and the registry entry does not describe the randomization method, sequence generation, or concealment procedure.

This record labels the design randomized and parallel-group, while also listing five treatment sequences that vary treatment across attack periods. The record does not explain how the parallel-group label relates to those sequences or how participants were allocated among them. The sequence descriptions alone do not establish the exact analysis model or whether observations from different periods were treated as independent.

What does masking mean in this record?

Masking is intended, in general, to reduce the influence of treatment knowledge on behavior, assessment, or interpretation. The official title calls the study triple-blind, whereas the registry’s masking entry says double. Since the record does not explain the discrepancy or specify which parties were masked, it is not possible to give a more precise account of masking based on this entry alone. Masking should not be assumed to eliminate all sources of bias.

How should a binary endpoint be understood?

The primary endpoint is a count of participants meeting a stated threshold: headache severity falls from moderate or severe at baseline to no headache or mild headache at 2 hours. Such an outcome is binary for each participant. A group count describes the number meeting the threshold; a comparison requires both groups’ outcome data and a defined effect measure. Depending on the measure, results might be expressed as a difference in proportions, a ratio, or another contrast, but no such estimate is reported in this registry entry.

General statistical interpretation also considers uncertainty. A confidence interval gives a range of effect estimates compatible with the data and the method used, under its assumptions. It is not a guarantee that the true value lies in that range, and its width reflects precision as well as the analysis. No confidence interval for the primary endpoint is reported, so the record does not support an assessment of its precision.

Why do repeated attack periods matter?

When outcomes are measured across more than one period for a participant, observations may be related. In general, treating related observations as independent can misstate uncertainty. A suitable analysis may need to account for repeated measurements, treatment sequence, or period effects, depending on the design and estimand. The registry record lists efficacy outcomes for four attack periods and five sequences, but it does not report the statistical model or its handling of these features. It would be inappropriate to assume a particular repeated-measures or crossover method.

The design description also does not specify whether the primary comparison targets the first period alone, an average across periods, or another contrast. The primary endpoint title points to the first attack period, but the statistical plan and estimand are not reported. This distinction matters because the same sequence can expose a participant to different treatments at different periods.

What does the missing-data description tell us?

The primary efficacy analysis used an all-patients-treated approach that included participants with at least one efficacy measure after the initial dose. Missing values were imputed by carrying forward the preceding values in the same phase. This is a form of last-observation-carried-forward imputation, only in general terms: an observed value is used as a substitute for a later missing value within the specified phase.

Such an approach makes an assumption about what the missing outcome would have been. If the unobserved value differs systematically from the carried-forward value, the resulting estimate may be biased. The direction and magnitude of any bias depend on why values are missing and how outcomes change over time. The registry does not report the amount or pattern of missingness, the assumptions used to justify this method, or sensitivity analyses comparing alternative approaches.

What can be concluded from the safety counts?

The registry reports participants affected and at risk for serious and other adverse events. These counts are descriptive. General comparisons of adverse-event counts can be affected by differences in exposure time, event ascertainment, definitions, and analysis populations; the record does not provide enough detail to evaluate those features. The serious adverse event counts are zero in both listed groups, but that does not imply that all forms of harm were absent. Other adverse events are listed separately, and the entry does not provide their terms.

Finally, a sample-size calculation based on an observed effect is a planning illustration, not observed power. It describes a hypothetical future design under stated assumptions. The registry record does not report the trial’s own sample-size justification, and the primary efficacy effect needed to interpret any effect-based illustration is not posted. No planning calculation can substitute for the missing efficacy result or establish that the trial had a particular probability of detecting an effect.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome for pain relief at 2 hours during the first migraine attack period and secondary outcomes for the second, third, and fourth periods. Considering several outcomes or time points raises a general multiplicity issue: when many statistical tests are conducted, the chance of at least one apparently unusual result can increase unless the analysis plan addresses that concern. The registry record does not report whether multiplicity was controlled, which outcomes were formally tested, or whether a hierarchical testing procedure was planned.

The record identifies the primary analysis population as an all-patients-treated approach. It included participants with at least one efficacy measure after the initial dose, with missing values imputed by carrying forward preceding values in the same phase. This describes the stated handling of missing efficacy measures, but the record does not give the number or pattern of missing values, reasons for missingness, or sensitivity analyses. The assumptions behind carrying values forward cannot be checked from the posted entry.

Other analysis-population details are not reported in the registry record. It does not give the number analyzed for the primary efficacy outcome, the group-specific efficacy denominators, or exclusions after enrollment. The safety counts have their own at-risk denominators and should not be assumed to match the efficacy population.

The record does not report the statistical plan, interim analyses, prespecified handling of multiple attack periods, or a primary effect estimate. These gaps mean the relationship between the listed outcomes and any formal testing strategy cannot be reconstructed. The presence of several outcome time points alone does not establish that a multiplicity adjustment was necessary or that one was applied; the details are not reported in the registry record.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious and other adverse events separately. For serious adverse events, 0 of 337 participants at risk in the rizatriptan 10 mg group were affected, and 0 of 84 participants at risk in the placebo group were affected. For other adverse events, 199 of 323 participants at risk in the rizatriptan group were affected, compared with 31 of 84 at risk in the placebo group. These are counts as recorded, not calculated percentages.

The at-risk denominators differ between the serious and other adverse event entries for the rizatriptan group. The registry does not explain why, so these counts should be read with their own stated denominators rather than treated as if they came from identical sets of participants. The record does not report descriptions or terms for the other adverse events, and serious adverse event terms are not reported in the registry record. Death counts are not reported in the registry record.

These descriptive safety figures do not provide information about event timing, duration, severity beyond the serious-event classification, relatedness to treatment, or exposure-adjusted rates. The record also does not provide uncertainty estimates or a formal comparison. Zero recorded serious adverse events in the listed groups does not establish that no serious events could occur or that the treatments have equivalent safety. The counts should be interpreted as registry-recorded observations, not as a complete account of safety.

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

The registry record documents a randomized phase 3 study of rizatriptan benzoate and placebo for treatment across multiple acute migraine attack periods. Its primary endpoint is defined as pain relief at 2 hours in the first period, and the primary efficacy population and missing-value approach are described. These details clarify what the planned outcome represents, but they do not show the comparative efficacy result.

No group-specific primary outcome counts, effect estimate, confidence interval, or p-value are reported. The registry record lists no analyses. Therefore, it is not possible to state from this record how the primary outcome differed between the treatment conditions or how precisely any difference was estimated. Missing efficacy results should not be interpreted as evidence of no difference, nor as evidence of a benefit.

The recorded safety counts show zero participants affected by serious adverse events in both listed groups, alongside other adverse event counts of 199 of 323 at risk for rizatriptan and 31 of 84 at risk for placebo. Those observations do not establish a complete safety profile or explain the nature of the other adverse events. The registry does not provide event terms, death counts, or a formal safety comparison.

The record also leaves important design and analysis details unresolved, including the discrepancy between the title’s triple-blind description and the double-masking entry, the allocation among treatment sequences, and the statistical handling of multiple attack periods. These unknowns limit how fully the design and analysis can be evaluated.

In general, a trial’s design, endpoint, estimate, and uncertainty all contribute to interpretation. Here, the design and endpoint are described, but the efficacy estimate and its uncertainty are not reported. The appropriate conclusion is limited to what the registry documents: the study was completed and its record contains design information and selected safety counts, while the primary efficacy result remains unavailable in the registry record.

13. Why This Trial Matters Statistically

This study raises statistical questions that arise when a clinical trial evaluates outcomes across multiple treatment periods. The registry lists five sequences that place placebo in different attack periods or use rizatriptan throughout. This makes the timing and sequence of exposure relevant to interpreting outcomes. A statistical analysis must match the design and clarify which treatment contrast it estimates; the registry record does not report how this was done.

The endpoint definition also illustrates how a continuous symptom experience can be represented as a threshold-based binary outcome. Such thresholds can be straightforward to explain, but they do not capture every degree of change. The record defines relief through a shift between specified headache grades, yet does not post the resulting participant counts. This is a reminder that a clearly specified endpoint is not the same as a reported result.

Repeated measures and missing observations are further considerations. The primary analysis used carrying forward of preceding values within the same phase, while outcomes were defined across multiple attack periods. In general, both the dependence among repeated observations and assumptions about missing values can affect an estimate and its uncertainty. The statistical plan and sensitivity analyses are not reported, so the robustness of an efficacy analysis cannot be evaluated.

The record’s completed status and detailed endpoint label might suggest that a result should be available, but completion alone does not provide an estimate. With no posted primary comparison, readers cannot judge magnitude, precision, or the relationship between the primary and secondary outcomes. Statistically, the record is most useful as an example of why design descriptions, analysis methods, and results all matter—and why safety counts cannot replace an unreported efficacy analysis.

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 main limitation of the registry record for interpreting efficacy is that it does not report the primary outcome counts or comparative estimate. It also gives no confidence interval or p-value, and lists no analyses. The result’s magnitude and precision therefore cannot be assessed from the posted record. The secondary outcome results for later attack periods are not reported either.

Several design details are unclear. The official title calls the study triple-blind, while the registry masking entry says double; the record does not reconcile these descriptions. It lists randomized, parallel-group design features and five treatment sequences, but does not explain allocation among sequences or how multiple attack periods entered the analysis. The randomization procedure, concealment, and identities of masked parties are not reported in the registry record.

The missing-data description is limited to carrying forward preceding values within the same phase. The record does not provide the extent or reasons for missingness, or sensitivity analyses that test the implications of this choice. It also does not report the detailed statistical plan, multiplicity handling, interim analyses, or the trial’s sample-size justification. These omissions prevent a thorough appraisal of prespecification and robustness.

Safety interpretation is also constrained. Other adverse events are reported as counts without event terms, and the registry does not report death counts. The different at-risk denominators across serious and other adverse event entries for rizatriptan are unexplained. There are no uncertainty estimates or formal comparisons for these counts.

These limitations describe what is and is not reported in the registry record; they do not establish that the omitted information was never collected or analyzed. They do mean that the posted entry alone cannot support a full efficacy or safety assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treatment of Multiple Attacks of Acute Migraine (0462-025) — NCT00899379.
• Registry record last updated 2022-02-03; status last verified 2022-02.
• Results first posted 2010-07-15.
• 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

NCT00899379 is a completed phase 3 randomized study of rizatriptan benzoate and placebo for multiple acute migraine attacks. The registry reports 473 enrolled and describes five treatment sequences across attack periods. The primary endpoint is the number of participants with pain relief at 2 hours during the first period, using a specified reduction in headache severity. The primary analysis included participants with at least one efficacy measure after the initial dose and carried preceding values forward for missing data within the same phase.

The registry record does not report primary or secondary efficacy results, an effect estimate, or uncertainty measures, and it lists no analyses. Safety entries report serious and other adverse event counts, but provide limited event detail. The record does not explain the title’s triple-blind description alongside its double-masking entry or provide the statistical plan. Accordingly, the design and endpoint can be described, but the primary efficacy comparison cannot be interpreted from the posted record.