A Study to Evaluate the Efficacy and Tolerability of Rizatriptan for Treatment of Acute Migraine (0462-087): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy and Tolerability of Rizatriptan for Treatment of Acute Migraine (0462-087) (NCT00894556), a randomized phase 3 study. The primary outcome is Pain Relief (PR).

2. Clinical Question

3. Trial Design

The registry record describes a phase 3, randomized, double-blind, placebo-controlled crossover trial. It lists enrollment of 109 participants and a completed study. The recorded start date is 2009-06-10, and the primary completion date is 2010-01-12. The sponsor is Organon and Co.

A crossover design exposes participants to more than one treatment over successive periods. In this trial, the recorded sequences were rizatriptan, rizatriptan, then placebo; rizatriptan, placebo, then rizatriptan; and placebo, rizatriptan, then rizatriptan. A baseline phase is identified as sumatriptan. The registry record does not report the length of the periods, the interval between them, or details about how attacks were allocated to treatment periods.

General statistical context: a crossover design can compare treatments within the same participant, which may reduce the influence of stable differences between participants. Its interpretation also depends on period and sequence effects, and on whether treatment effects carry into later periods. The registry record does not report how these issues were assessed or incorporated into the analysis. Randomization and double masking are stated, but the randomization procedure and masking details are not reported in the registry record.

The trial's official title identifies the target group as sumatriptan non-responders, and the brief summary says it aimed to provide evidence concerning rizatriptan in people with an inadequate response to sumatriptan. The specific criteria used to define inadequate response, and the process for determining eligibility, are not reported in the registry record. The listed treatment sequences establish that placebo was included, but do not by themselves identify the exact statistical comparison used for the primary outcome.

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: Participants who met entry criteria but had evidence of suicidality or were severely depressed (based on questionnaire scores) were excluded. Within 2 months of entry, participants were to treat a moderate/ severe migraine attack with sumatriptan 100 mg and were randomized if they still had moderate or severe pain at 2 hours post-dose.

Baseline Phase

Reasons for not completing this period:

Treatment Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The FAS population included all randomized participants who had at least one evaluable attack. To be considered an evaluable attack the participant must have administered study treatment for this attack and must have had both a baseline severity measurement and at least one post-dose efficacy measurement prior to or including the 2-hour time point.

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 (PR), measured over 2 hours post dose.

The primary endpoint was pain relief, recorded as a number of attacks and assessed 2 hours post dose. Participants rated headache severity in a paper diary on a scale from 0 (no pain) to 3 (severe pain), with 1 representing mild pain and 2 moderate pain. Pain relief was defined as a reduction from Grade 3 or 2 at baseline to Grade 1 or 0 after dosing.

This endpoint expresses a change in headache severity rather than a single post-dose rating. Such a definition is useful for distinguishing attacks that improve to mild or no pain from those that remain moderate or severe. The registry record does not state whether the reported count refers to attacks meeting the definition, how counts were summarized for each participant, or which treatment contrast was used to analyze them.

The registry record identifies the endpoint and its assessment time but does not report the numerical outcome, an effect estimate, or a measure of uncertainty. Therefore, the endpoint definition can be described, but the degree of observed pain relief and the precision of any treatment comparison cannot be assessed from the posted results. Pain Freedom (PF) is listed as a secondary outcome; its definition and numerical result are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: statistical interpretation begins with a clearly defined estimand—the treatment effect the analysis is intended to estimate, in a specified population, for a specified outcome and time. For this trial, the registry identifies pain relief as the primary outcome, defines the response using changes in headache severity, and states that assessment occurred 2 hours post dose. It does not report a single treatment contrast or a numerical estimate. Consequently, the precise estimand cannot be reconstructed from the registry entry.

What does the crossover design imply?

In a crossover trial, participants receive treatments in different periods according to assigned sequences. The registry lists three sequences involving rizatriptan and placebo, along with a sumatriptan baseline phase. General statistical context: because the same participant can contribute information under multiple treatments, a suitable analysis may account for within-participant pairing. This can distinguish treatment differences from stable participant-level differences. The registry record does not report whether a paired method was used, how participant-level observations were summarized, or how observations from different periods were modeled.

Period and sequence can matter in crossover studies. General statistical context: outcomes may change over time for reasons unrelated to treatment, and an effect from an earlier treatment may persist into a later period. Methods can account for these possibilities if the design and data support doing so. The registry record does not report the period lengths, any washout interval, tests for carryover, or adjustment for period or sequence. It would therefore be inappropriate to assume that these factors were assessed or that a particular crossover analysis was used.

How should the endpoint be understood?

The primary endpoint is described as a number of attacks meeting a pain-relief definition. Headache severity was rated in a paper diary from 0, no pain, through 3, severe pain. A qualifying reduction was from Grade 3 or 2 at baseline to Grade 1 or 0 after dosing. General statistical context: when an endpoint is a count, the analysis can depend on how often participants contribute observations and how variable those counts are. A count of attacks is not automatically equivalent to a proportion of participants responding. The registry record does not state the precise summary or model used for the primary analysis, so the outcome should not be reinterpreted as a participant-level response rate.

The record lists Pain Freedom (PF) as a secondary outcome, but does not give its definition or results. It reports two outcome measures and two analyses, without describing the analysis methods or identifying a complete set of contrasts. The primary outcome is explicitly not reduced to one comparison because it has several categories or time points. This makes it especially important to distinguish the endpoint definition from the statistical question addressed by any particular analysis.

What does an uncertainty estimate tell a reader?

General statistical context: an effect estimate describes the observed difference or contrast under a particular analysis, while a confidence interval describes the range of values reasonably compatible with the data and that analysis. A narrow interval indicates greater precision than a wide interval, but precision does not by itself establish clinical importance. The registry record does not report an effect estimate or confidence interval for the primary outcome. Statistical significance, the size of the effect, and its precision therefore cannot be evaluated from the posted results.

The record also does not report a primary-outcome p-value. A p-value, in general, measures how incompatible the observed data are with a specified null model, assuming the model and analysis are appropriate. It does not indicate the probability that a treatment is effective or the probability that the null hypothesis is true. Without the test result, the null hypothesis, and a clear account of the comparison, no p-value interpretation is possible for the primary endpoint.

What do the planning assumptions mean?

The registry describes sample-size figures as planning illustrations computed from the observed effect, not as the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. For non-time-to-event outcomes, the stated interpretation is participants per arm for a specified power level. These are planning assumptions, not observed trial outcomes and not observed power.

General statistical context: a planning calculation asks how much information might be required under specified assumptions to detect an effect of a chosen size. Its output changes when those assumptions change. It cannot establish that the trial had a particular probability of success after the results are known. The numerical planning outputs and the observed effect on which they are based are not reported in the registry record. Nor does the record report its original sample-size justification. The listed enrollment of 109 should not be treated as evidence that a particular power target was met.

What remains unknown about the analysis?

The record does not report the statistical model, the unit of analysis, the method for handling repeated attacks, or how correlation within participants was addressed. It does not describe adjustment for baseline severity, treatment sequence, or period. It also does not report a prespecified analysis plan or whether any analyses were changed. These omissions do not show that the issues were ignored; they mean the registry record does not document how they were handled.

The registry reports the full analysis set definition: all randomized participants with at least one evaluable attack, where the attack had to involve study treatment, a baseline severity measurement, and at least one post-dose efficacy measurement. This is useful for understanding which observations could qualify, but the number of participants and attacks actually analyzed is not reported. The approach to missing diary entries, incomplete periods, and other missing outcome data is also not reported. No uncertainty estimates for the efficacy results are available to assess how much information the analysis contained.

10. Multiplicity, Missing Data and Analysis Populations

The registry record identifies pain relief as the primary outcome and Pain Freedom (PF) as a secondary outcome. It also states that the primary outcome has several categories or time points and was not reduced to one comparison. Two outcome measures and two analyses are listed, but the analysis descriptions are not reported in the registry record. The record does not specify which contrasts were treated as primary, how many tests were performed, or whether any adjustment for multiple testing was used.

General statistical context: when several outcomes, time points, or treatment contrasts are examined, the chance of at least one apparently unusual result can increase if each is tested separately. Multiplicity procedures can control or describe that issue, but they depend on a prespecified testing strategy. Since the registry does not report such a strategy or the efficacy results, it is not possible to assess how multiplicity affected interpretation. The absence of a reported adjustment should not be taken as evidence that no adjustment was made.

The full analysis set is described as randomized participants with at least one evaluable attack. That definition requires study treatment for the attack, a baseline severity measurement, and at least one post-dose efficacy measurement. The registry does not report the number of participants or attacks excluded by these criteria, the primary analysis count, or the treatment of participants with incomplete crossover data.

The handling of missing diary measurements and other missing data is not reported in the registry record. It does not state whether missing values were omitted, imputed, or addressed through another method. The analysis population beyond the stated full analysis set, including whether a separate per-protocol or safety population was used, is not described. Interim analyses and a protocol-based statistical analysis plan are also not reported in the registry record. These are documentation gaps; they do not establish what analyses were or were not performed.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry records no serious adverse events affecting participants in the rizatriptan 10 mg group, placebo group, or sumatriptan 100 mg group. The corresponding numbers at risk are 102, 100, and 194. Serious adverse event terms are not listed. Death counts are not reported in the registry record; an unreported count should not be read as a count of zero.

Other adverse events are recorded as affecting 18 in the rizatriptan 10 mg group, 3 in the placebo group, and 29 in the sumatriptan 100 mg group. These are counts, and no comparative analysis or uncertainty measure is reported. They should not be treated as percentages or as evidence of a causal treatment difference. The record does not explain how these safety group denominators relate to the crossover treatment periods, so the groups should not be assumed to represent independent sets of participants.

General statistical context: safety counts are most informative when the event definition, exposure period, denominator, and method of attribution are clear. The registry provides group counts and numbers at risk but does not give detailed event descriptions or explain the denominator structure. The figures therefore describe what was recorded, while leaving important questions about exposure and comparability unresolved.

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

The registry record documents a randomized, double-blind, placebo-controlled crossover study of rizatriptan 10 mg for acute migraine in people described as sumatriptan non-responders. It gives the treatment sequences, identifies pain relief as the primary outcome, and defines relief as a reduction from moderate or severe headache at baseline to mild or no pain after dosing. It also records a 2-hour assessment time and describes the full analysis set eligibility criteria.

Those details explain what the study was designed to examine, but they do not establish what the primary comparison found. The numerical result, treatment-specific summaries, effect estimate, uncertainty interval, and primary-outcome p-value are not reported in the registry record. Therefore, the posted results do not support a conclusion about the direction or magnitude of an efficacy difference, or the precision of such a difference. The absence of a reported estimate is not evidence that the treatments were equal, and it is not evidence that one was better.

The safety information is also limited. The registry records no serious adverse events in the listed groups and records other adverse events affecting 18, 3, and 29 in the rizatriptan, placebo, and sumatriptan groups, respectively. These figures are descriptive and lack a documented comparison method. Death counts are not reported in the registry record. The safety counts alone cannot establish a treatment-related effect.

General statistical context: an outcome definition, a study design, and an enrollment count are not substitutes for the results of the planned comparison. Interpretation requires knowing what was estimated, how the data were analyzed, how much uncertainty remains, and which participants and observations contributed. The record leaves these points unresolved for the primary outcome.

Accordingly, the registry entry can support a description of the trial's stated question and design, but not a firm statistical conclusion about the primary efficacy result or comparative safety. This interpretation concerns the documentation in the registry record; it does not make a clinical recommendation.

13. Why This Trial Matters Statistically

This trial is statistically notable for its crossover structure. The randomized sequences placed participants on rizatriptan and placebo in different periods, while the registry also identifies a sumatriptan baseline phase. In general, crossover designs can make within-participant comparisons possible, but they also require attention to period, sequence, and potential carryover. The registry describes the sequence structure but does not report how the analysis handled those design features.

The primary outcome is defined at the attack level: pain relief is based on a change in headache severity, and the outcome is recorded as a number of attacks. That distinction matters because counts of attacks are not automatically interchangeable with proportions of participants experiencing relief. The record does not describe how repeated attacks were summarized or modeled, leaving the unit of analysis and the handling of within-participant correlation unclear.

The record also illustrates why outcome definitions and results must be read separately. It gives a detailed response definition and assessment time, but the primary numerical result is not reported. It notes that the outcome involved several categories or time points and was not reduced to a single comparison. Without the contrast, estimate, and uncertainty, the endpoint description cannot answer the statistical question by itself.

Finally, the stated planning calculations are illustrations based on an observed effect and specified assumptions, not evidence of observed power or the trial's original design rationale. The original sample-size justification is not reported in the registry record. Distinguishing planning assumptions from trial results is important when interpreting what an enrollment of 109 can and cannot establish.

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 statistical interpretation is the absence of a numerical primary outcome result. The registry record does not report treatment-specific pain-relief counts, the primary comparison, an effect estimate, an uncertainty interval, or a p-value. Although it defines the outcome and its assessment time, it does not provide enough information to judge the size or precision of any efficacy difference.

The primary outcome is described as involving several categories or time points and is not reduced to one comparison. The registry does not identify the intended contrast or explain how those categories and time points were handled. The analysis model and unit of analysis are also not reported. For a crossover study with attacks observed across treatment periods, the absence of details about participant pairing, repeated observations, period effects, sequence effects, and carryover limits interpretation of the design's statistical implementation.

The record states a full analysis set definition, but does not report how many participants or attacks met it, how many contributed to each treatment period, or how incomplete crossover participation was handled. The approach to missing diary data and other missing outcomes is not reported. The number enrolled therefore does not reveal the amount of analyzable information for the primary endpoint.

Multiplicity procedures, interim analyses, and the original sample-size justification are not reported in the registry record. The listed planning illustrations are based on the observed effect and stated assumptions, but their numerical outputs and the observed effect are not reported. They cannot resolve the missing efficacy results or establish the trial's planned power.

Safety interpretation is constrained by limited detail about event definitions and the relationship between the group denominators and the crossover periods. Serious adverse events are recorded as zero in the three groups, while death counts are not reported. Other adverse events are reported as counts without comparative uncertainty estimates. These limitations concern what the registry documents and do not determine what may be available in other trial materials.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy and Tolerability of Rizatriptan for Treatment of Acute Migraine (0462-087) — NCT00894556.
• Registry record last updated 2024-05-10; status last verified 2022-02.
• Results first posted 2011-01-20.
• 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 a completed phase 3 randomized, double-blind, placebo-controlled crossover trial sponsored by Organon and Co. It lists 109 enrolled participants, a start date of 2009-06-10, and a primary completion date of 2010-01-12. The official title identifies acute migraine in sumatriptan non-responders as the study context.

The treatment sequences involved rizatriptan 10 mg and placebo, with sumatriptan identified as the baseline phase. The primary outcome was pain relief, defined by a reduction in headache severity at 2 hours post dose and recorded as a number of attacks. Pain Freedom (PF) is listed as a secondary outcome. The full analysis set included randomized participants with at least one evaluable attack.

The registry does not report a numerical primary efficacy result, a treatment contrast, or an uncertainty estimate. It records no serious adverse events in the listed groups and gives other adverse event counts, but does not provide a comparative safety analysis. Key details of the crossover analysis, missing-data handling, multiplicity strategy, and original sample-size justification are not reported in the registry record.