A Study of Rizatriptan for the Treatment of Acute Migraine in Patients on Topiramate for Migraine Prophylaxis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Rizatriptan for the Treatment of Acute Migraine in Patients on Topiramate for Migraine Prophylaxis (NCT00812006), a randomized phase 3 study. The primary outcome is Pain Relief (PR).

2. Clinical Question

This question concerns acute treatment during ongoing migraine prophylaxis, rather than topiramate itself. The trial record describes a randomized, double-blind crossover design, so treatment was organized in sequences rather than as a simple assignment to one treatment for the entire study. The listed sequences include both rizatriptan and placebo occasions.

The registry record lists 108 participants enrolled. It does not report the number who contributed evaluable attacks to the primary analysis or how many attacks each participant contributed. Those details matter when interpreting an attack-based outcome: the number of attacks is not necessarily the same as the number of participants, and repeated attacks from one participant may be statistically related.

3. Trial Design

NCT00812006 is recorded as a Phase 3, randomized, double-blind, placebo-controlled crossover trial sponsored by Organon and Co. The record lists a start date of 2009-03-24, a primary completion date of 2009-10-22, and a completed status. Enrollment was 108.

The study examined rizatriptan for acute migraine in patients taking topiramate for migraine prophylaxis. The official title specifies rizatriptan 10 mg ODT. The comparator was placebo. Rather than assigning participants to a single treatment group, the record lists three randomized sequences: two occasions with rizatriptan followed by placebo; rizatriptan, placebo, then rizatriptan; or placebo followed by two rizatriptan occasions. The registry record does not report how long separated the treatment occasions or how sequence assignment was balanced.

In a crossover design, participants receive more than one treatment over the study. General explanation: this design can allow comparisons that account for stable differences between participants, because a participant may contribute observations under both treatments. It also requires care with the order and timing of treatments, as well as the possibility that an earlier treatment could affect a later observation. The registry record does not report the methods used to account for period or sequence effects, or whether carryover was assessed.

The primary outcome was pain relief, measured in attacks at 2 hours post dose. Secondary outcomes were Sustained Pain Relief, Pain Freedom, Normal Rating of Functional Disability, and Treatment Satisfaction. The record lists five outcome measures and five analyses, but does not give a single overall primary comparison in the posted outcome information. The study’s statistical analysis plan, including the model used for the crossover data, is not reported in the registry record.

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 were assessed, using the protocol inclusion and exclusion criteria, at Visit 1, and if eligible, were randomized at the same visit.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set, which 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 have both a baseline severity measurement and at least one post-dose efficacy measurement at or prior to 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 is Pain Relief (PR), measured as the number of attacks at 2 hours post dose. Participants recorded pain severity in a paper diary on a scale from 0 (no pain) to 3 (severe pain), with 1 denoting mild pain and 2 moderate pain. An attack met the registry definition of pain relief if severity moved from Grade 3 or 2 at baseline to Grade 1 or 0 after dosing.

This endpoint captures a change in headache severity rather than requiring complete absence of pain. General explanation: a prespecified threshold can make an endpoint easier to interpret by distinguishing a meaningful category of response from no response, while still retaining a broader definition than pain freedom. Pain Freedom is listed separately as a secondary outcome.

The registry record defines the Full Analysis Set as randomized participants with at least one evaluable attack. An attack was considered evaluable if the participant administered study treatment and had a baseline severity measurement and at least one post-dose efficacy measurement. The primary outcome is expressed in attacks, so its interpretation depends on how attacks were counted and analyzed, particularly if participants contributed repeated observations.

The registry record does not report the primary endpoint results as a single comparison, nor does it give an effect estimate or uncertainty interval. The measure is therefore identifiable, but its comparative result cannot be interpreted from the posted primary-outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a randomized, double-blind crossover trial. Randomization assigns participants to treatment sequences, while blinding is intended to keep treatment identity masked during the study. The listed sequences each include rizatriptan and placebo occasions. The record does not describe the specific randomization procedure, who was masked, or how masking was maintained.

What does crossover mean for the comparison?

General explanation: in a crossover study, a participant can receive more than one study treatment at different occasions. Comparisons may then use information from the same participant under different treatments, which can reduce the influence of stable differences between participants. However, observations from the same person are related rather than independent. The analysis should account for this dependence. Treatment order and time can also matter: an observation may be affected by the occasion on which treatment was given, or by an earlier treatment. The registry record does not report the analysis model, any washout arrangements, or whether period, sequence, or carryover effects were assessed.

The outcome is attack-based. Participants rated pain in a paper diary, and pain relief was defined by a shift from moderate or severe pain at baseline to mild or no pain after dosing. The endpoint timeframe was 2 hours post dose. The registry record does not report whether the primary analysis used participant-level summaries, attack-level observations, or another approach. It also does not report how dependence among multiple attacks from one participant was handled.

How should an effect estimate and confidence interval be read?

General explanation: an effect estimate describes the treatment contrast under the chosen analysis, while a confidence interval expresses the uncertainty around that estimate. A narrower interval indicates greater precision under the assumptions of the analysis; a wider interval indicates less precision. The interval does not remove concerns about missing observations, model choice, or bias. The registry record does not report a primary effect estimate or confidence interval for this outcome, so the treatment contrast’s magnitude and precision cannot be assessed from the posted primary results.

A p-value, when reported, addresses how compatible the observed data are with a specified null hypothesis under the analysis assumptions. It does not measure the size or clinical importance of an effect. No primary p-value is reported as a single comparison in this record. It would therefore be inappropriate to infer statistical significance or lack of significance from the endpoint description or enrollment count.

What do the planning assumptions mean?

General explanation: sample-size calculations are planning exercises that depend on an assumed effect, variability, significance level, allocation, and analysis method. The registry record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration considers effects stated as fractions of the observed effect. These assumptions describe the illustration, not necessarily the trial’s original design. The registry record does not report the trial’s own sample-size justification or the assumed effect used when planning the study.

Any participant counts from such an illustration would be planning quantities, not observed power. Observed power is not a substitute for an effect estimate and its uncertainty. The registry record does not report a single primary comparison from which to judge the observed effect in this analysis. The planning assumptions therefore cannot fill the gap in the reported outcome results.

Why can over-dispersion matter?

General explanation: count outcomes can vary more than a simple statistical model expects. This is called over-dispersion. If it is ignored, standard errors may be too small and confidence intervals too narrow. For this trial, the primary outcome is described as a number of attacks, but the registry record does not give the model or dispersion assumptions used for analysis. It is therefore not possible to assess from the record whether over-dispersion was considered.

These statistical concepts help explain what information is needed to interpret the design: a defined estimand, a model suited to repeated attack data, a treatment contrast, and uncertainty around that contrast. The registry record identifies the clinical endpoint and trial structure, but does not report these analysis details or a single primary result.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures and five analyses. It names Pain Relief as primary and lists Sustained Pain Relief, Pain Freedom, Normal Rating of Functional Disability, and Treatment Satisfaction as secondary outcomes. The record also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. It does not report how the primary endpoint’s categories or time points were handled in the analysis.

When multiple outcomes, time points, or comparisons are tested, the chance of at least one apparently notable result can increase. General explanation: statistical methods for multiplicity can control or otherwise address this issue, but the appropriate approach depends on which comparisons were prespecified and how they were prioritized. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a detailed analysis plan. It is not possible to determine whether or how multiplicity was addressed.

The Full Analysis Set included randomized participants who had at least one evaluable attack. An evaluable attack required treatment administration, a baseline severity measurement, and at least one post-dose efficacy measurement. This definition clarifies a minimum for inclusion, but the registry record does not report the number of participants or attacks excluded, the reasons for missing measurements, or how missing data were handled. It also does not report sensitivity analyses for missing outcomes.

The record does not report whether all randomized participants were included in the primary analysis under their assigned sequence, or how deviations from the planned treatment occasions were handled. These analysis-population and missing-data details are important for assessing the robustness of a crossover comparison.

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 record reports serious adverse events for the treatment groups as counts among participants at risk. For rizatriptan, 101 were at risk and 0 were affected by a serious adverse event. For placebo, 94 were at risk and 0 were affected by a serious adverse event. The record does not report deaths; the death entries are not reported in the registry record.

For other adverse events, the record lists 101 at risk and 16 affected for rizatriptan, and 94 at risk and 3 affected for placebo. These are descriptive counts. The record does not provide event terms, severity classifications for these other events, exposure time, or an inferential comparison. It also does not explain how the at-risk groups were defined in relation to the crossover sequences.

Zero recorded serious adverse events in these groups does not establish that serious events cannot occur, and the raw counts alone do not quantify a comparative safety effect. General explanation: safety comparisons depend on the events collected, the observation period, participant exposure, and the analysis used. The registry record does not provide enough detail to assess those factors or to interpret the counts as a formal test of difference.

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

The registry record describes a randomized, double-blind, placebo-controlled crossover trial of rizatriptan for acute migraine attacks in people taking topiramate for migraine prophylaxis. It specifies the pain-relief definition, the 2-hour post-dose assessment, and the Full Analysis Set eligibility criterion. These details identify what the primary outcome was intended to measure and which attacks could contribute to the analysis.

They do not establish the comparative result. The record does not report a single reduced primary-outcome comparison, an effect estimate, or its uncertainty. It is therefore not possible to say from the posted primary results how large the pain-relief contrast was, how precise it was, or whether the data supported a difference under the trial’s analysis.

The enrollment count of 108 is not the same as the number of participants or attacks included in the primary analysis. The Full Analysis Set required at least one evaluable attack, but its size and the number of contributing attacks are not reported. The analysis method for repeated attacks and treatment occasions is also not reported. These details affect how much information the observed comparison would contain and how its uncertainty should be estimated.

The adverse-event counts provide descriptive information: no serious adverse events were recorded among the reported at-risk groups, while other adverse events were reported for both treatments. They do not, on their own, establish a comparative safety conclusion. The registry record does not supply event-level descriptions or an inferential analysis.

Thus, the record can support an explanation of the study question, design, endpoint, and reported adverse-event counts. It cannot support a conclusion about the magnitude, precision, or statistical significance of the primary treatment contrast. The missing outcome results should not be replaced by assumptions based on the design, the endpoint definition, or the planning illustration.

13. Why This Trial Matters Statistically

This trial raises statistical issues that are common in acute-treatment studies with repeated observations. The outcome is counted in attacks, but participants may contribute more than one attack. Such observations can be correlated within a person, so the analysis needs to reflect the data structure rather than treating every attack as unrelated. The registry record does not report how that dependence was handled.

The crossover design adds another layer. Each listed sequence includes both rizatriptan and placebo occasions, allowing within-participant information to be relevant to a treatment comparison. General explanation: this can be useful when stable participant characteristics affect outcomes, but the analysis must also account for treatment order and possible period or carryover effects. The registry record does not report the model or the checks used to address these issues.

Endpoint definition also matters. Pain relief was defined by a change in a four-category pain scale at 2 hours post dose, and the measure is expressed in attacks. That threshold is distinct from the separately listed Pain Freedom outcome. Keeping the endpoint definition clear prevents readers from treating partial relief and absence of pain as the same outcome.

Finally, a well-described design is not enough to assess an effect. Interpretation requires a reported treatment contrast and its uncertainty, along with information about the analysis population, missing observations, and multiplicity. The registry record gives useful details about the intended question but does not report a single primary comparison. That gap illustrates why the presence of a completed trial record and a defined endpoint cannot substitute for transparent outcome reporting.

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 registry record does not report a single primary-outcome comparison, effect estimate, confidence interval, or p-value. It indicates that the primary outcome has several categories or time points and was not reduced to one comparison. This prevents direct interpretation of the primary treatment contrast from the posted results.

Although the record describes a crossover design and three treatment sequences, it does not report the statistical model, how within-participant dependence was handled, or whether period, sequence, or carryover effects were considered. It does not state the timing between treatment occasions or provide a detailed account of treatment exposure. These omissions make it difficult to assess whether the analysis reflected the design.

The record reports enrollment of 108 but does not give the size of the Full Analysis Set or the number of evaluable attacks by treatment. It does not describe the extent or reasons for missing measurements, the method used to handle missing data, or sensitivity analyses. The primary population definition is available, but its implementation cannot be evaluated from the registry information.

Five outcome measures and five analyses are listed, but the record does not report a testing hierarchy or whether multiplicity was addressed. It also does not report the trial’s own sample-size justification. The planning illustration’s assumptions should not be interpreted as the study’s original design rationale or as observed power.

For safety, the record gives at-risk and affected counts but not event descriptions or an inferential comparison. It does not report deaths. Together, these reporting limitations restrict assessment of both the primary efficacy comparison and the context of the adverse-event counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Rizatriptan for the Treatment of Acute Migraine in Patients on Topiramate for Migraine Prophylaxis — NCT00812006.
• Registry record last updated 2024-05-23; status last verified 2022-02.
• Results first posted 2011-01-27.
• 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

NCT00812006 is a completed Phase 3 randomized, double-blind, placebo-controlled crossover trial sponsored by Organon and Co. It enrolled 108 participants and examined rizatriptan 10 mg ODT for acute migraine attacks in patients taking topiramate for migraine prophylaxis. The listed sequences included two rizatriptan occasions and one placebo occasion in differing orders.

The primary outcome was attack-level Pain Relief at 2 hours post dose, defined by a reduction from moderate or severe pain at baseline to mild or no pain after treatment. Secondary outcomes included Sustained Pain Relief, Pain Freedom, Normal Rating of Functional Disability, and Treatment Satisfaction.

The registry record does not report a single reduced primary comparison or its effect estimate and uncertainty. It reports no serious adverse events among the listed at-risk groups and gives counts for other adverse events, without a formal comparative analysis. Details about the primary analysis model, multiplicity, and missing-data handling are not reported in the registry record.