Safety and Efficacy Trial of BHV3000 (Rimegepant) 75 mg for the Acute Treatment of Migraine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Trial of BHV3000 (Rimegepant) 75 mg for the Acute Treatment of Migraine (NCT04574362), a randomized phase 3 study. The primary outcome is Percentage of Participants Who Had Freedom From Pain at 2 Hours Post-dose.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, quadruple-masked, parallel-group trial comparing rimegepant 75 mg with matching placebo for acute migraine. The registry lists enrollment of 1648. The study began on 2020-10-22, reached primary completion on 2021-11-24, and has a completed status. Pfizer is listed as the sponsor.

The registry summary says the trial was intended to assess safety and efficacy in Chinese and Korean patients. The active arm received one 75 mg oral disintegration tablet; the comparator arm received matching placebo. The record does not report the allocation ratio, details of sequence generation or concealment, the identities of the masked roles, or the criteria used to maintain masking. It also does not report the original sample-size justification or the trial’s planned assumptions for its design.

The primary efficacy analysis used a modified intent-to-treat population rather than every enrolled participant. To be included, participants had to be randomized, take study drug, have a moderate or severe migraine at treatment, and provide at least one post-treatment efficacy data point. This definition is important when interpreting the endpoint counts: the treatment-group denominators for the primary outcome were 666 and 674, rather than the overall enrollment figure. The registry does not report a full flow of participants through screening, randomization, treatment, and analysis.

Several secondary outcomes address pain relief, function, rescue medication use, duration of pain freedom, and early assessments after dosing. Their timing and definitions vary, so they should be read as distinct outcomes rather than interchangeable measures of the primary endpoint.

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 dispensed with 1 dose of study drug at randomization (baseline). Participants were required to administer pre-dispensed study drug only when the participants developed a migraine headache of moderate or severe intensity and completed all required migraine assessment questions in the electronic diary (eDiary), including their current most bothersome migraine symptom within 45 days of randomization.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified intent to treat (mITT) participants included all randomized participants who took study drug, had a migraine of moderate or severe intensity at the time of treatment, and provided at least 1 post-treatment efficacy data 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.

Population: Baseline analysis population included all treated participants (all enrolled participants who took either of the study drug).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Had Freedom From Pain at 2 Hours Post-dose, measured over 2 hours post-dose.

The primary endpoint was the percentage of participants with freedom from pain at 2 hours post-dose. Pain intensity was measured on a four-point Likert scale: 0 for none, 1 for mild, 2 for moderate, and 3 for severe. A score of 0 counted as freedom from pain. The endpoint therefore represents the proportion meeting a specific threshold at a fixed time, not a measure of average pain change or a description of how quickly pain improved.

A fixed-time binary endpoint gives a direct summary of how many participants in each arm met the stated criterion at the assessment. It can be compared between randomized groups, while retaining a clear clinical interpretation: whether the recorded pain score was zero at the specified assessment. The registry reports the percentage for each arm and an exact 95% confidence interval using the Clopper-Pearson method.

The analysis population was the modified intent-to-treat group. It included randomized participants who took study drug, had moderate or severe migraine at treatment, and posted at least one post-treatment efficacy data point. Thus, the endpoint results apply to that defined analysis population. The registry does not report how participants with missing pain assessments at the 2-hour time point were handled, or whether additional rules were used to classify them.

7. Results Posted in the Registry

• Rimegepant 75 mg: 19.8% (132/666) versus 10.7% (72/674) on control; risk difference 9.1 percentage points (95% CI 5.3 to 13.0), risk ratio 1.86 (1.42–2.42); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants With Pain Relief at 2 Hours Post-dose

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Rimegepant 75 mg: 66.5% (443/666) versus 48.5% (327/674) on control; risk difference 18.0 percentage points (95% CI 12.8 to 23.2), risk ratio 1.37 (1.25–1.51); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Rimegepant 75 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants Who Functioned Normally at 2 Hours Post-dose

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Rimegepant 75 mg: 40.7% (222/545) versus 23.8% (131/551) on control; risk difference 17.0 percentage points (95% CI 11.5 to 22.4), risk ratio 1.71 (1.43–2.05); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Rimegepant 75 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants Who Used Rescue Medication Within 24 Hours Post-dose

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Rimegepant 75 mg: 8.4% (56/666) versus 20.0% (135/674) on control; risk difference -11.6 percentage points (95% CI -15.3 to -7.9), risk ratio 0.42 (0.31–0.56); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Rimegepant 75 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes broaden the description of response beyond the primary pain-freedom endpoint. They include pain relief and normal function at 2 hours, rescue medication use within 24 hours, sustained pain freedom over later intervals, early pain or most-bothersome-symptom assessments, and pain relapse. These outcomes address related but distinct aspects of the post-dose experience, and their definitions and assessment times differ.

Among the secondary outcomes with numerical comparisons described in the registry results, pain relief and normal function at 2 hours were reported more often in the rimegepant arm than in the placebo arm. Rescue medication use within 24 hours was reported less often in the rimegepant arm. This pattern is directionally consistent with the primary pain-freedom comparison, while adding information about related outcomes. It does not establish that all listed secondary outcomes had the same pattern; individual results should be interpreted using their own estimates and uncertainty.

Secondary outcomes are generally less definitive when many outcomes are examined and no multiplicity adjustment or hierarchy is reported. Testing multiple endpoints creates more opportunities for a nominally small p-value to arise by chance. The registry record does not report whether the secondary outcomes were protected by a prespecified testing sequence or adjustment. Consequently, unadjusted secondary findings are best treated as supportive or descriptive rather than as independent confirmatory evidence.

The secondary endpoints also use different analysis populations and denominators. For example, the normal-function outcome has fewer participants in its arms than the primary endpoint, so its estimate concerns a different set of observations. Differences in eligibility, missing assessments, or endpoint definitions can influence the results. They should not be pooled mentally into a single measure of effect, and the secondary results do not replace the primary endpoint specified in the registry.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With Pain Relief at 2 Hours Post-dose
• Percentage of Participants Who Functioned Normally at 2 Hours Post-dose
• Percentage of Participants Who Used Rescue Medication Within 24 Hours Post-dose
• Percentage of Participants Who Sustained Pain Freedom From 2 to 24 Hours Post-dose
• Percentage of Participants Who Sustained Pain Freedom From 2 to 48 Hours Post-dose
• Percentage of Participants Who Had Freedom From Pain at 15, 30, 45, 60 and 90 Minutes Post-dose
• Percentage of Participants Who Had Freedom From MBS at 15, 30, 45, 60 and 90 Minutes Post-dose
• Percentage of Participants With Pain Relapse

9. Statistical Interpretation

10. Statistical Methods Explained

The main outcome is binary: each participant either met the endpoint definition or did not. For the primary endpoint, meeting the definition meant having a pain score of 0 at 2 hours post-dose. A percentage summarizes the share of participants who met that criterion in each arm. The comparison focuses on the difference between those shares, rather than on a change in the average pain score.

What does the risk difference express?

A risk difference is the percentage in one group minus the percentage in the comparison group, expressed on the probability scale. A positive risk difference for pain freedom means the recorded percentage was higher in the active-treatment group; a negative difference for rescue medication use means that the recorded percentage was lower in that group. The registry reports the primary risk difference as 9.2 percentage points. The unadjusted recalculation from the posted summary statistics is 9.14 percentage points. These estimates differ slightly because the registry’s reported result uses a Cochran-Mantel-Haenszel analysis, while the recalculation is a simple unadjusted comparison. The sponsor’s reported analysis takes precedence.

Risk differences are often straightforward to interpret because they retain the percentage-point scale of the endpoint. Other association measures, such as risk ratios and odds ratios, describe the same comparison on different scales. They can be useful for particular statistical questions, but can be less intuitive when communicating an absolute difference. The analysis presented for the primary outcome is the risk difference.

How should the confidence interval be read?

A confidence interval gives a range of values compatible with the observed data under a specified statistical method. It conveys estimation uncertainty: a narrower interval indicates greater precision, while a wider interval indicates less precision. It is not a range containing a fixed proportion of individual participant outcomes, and it is not a probability statement about the true effect after the data have been observed.

The registry used the Clopper-Pearson method for the exact 95% confidence intervals around the arm-level percentages. The reported between-group analysis used the Cochran-Mantel-Haenszel method for a risk difference. The record does not identify any strata or adjustment factors used in that analysis. The unadjusted recalculation uses posted arm-level summaries and does not reproduce any unreported stratification or adjustment.

What does the p-value add?

A p-value summarizes how incompatible the observed data are with a specified null hypothesis, assuming that hypothesis and the test’s other assumptions hold. The registry reports p < 0.001 for the primary comparison. This is evidence against a zero risk difference under the reported test. It does not quantify the size or practical importance of the difference, and it does not give the probability that the null hypothesis is true. The confidence interval and the arm-level percentages provide complementary information about magnitude and precision.

Why do analysis populations matter?

The primary analysis used the modified intent-to-treat population. This population required randomization, receipt of study drug, moderate or severe migraine at treatment, and at least one post-treatment efficacy data point. The denominators reported for the primary endpoint are 666 for rimegepant and 674 for placebo. The registry’s definition does not state how missing values at the exact 2-hour endpoint were treated, nor does it describe sensitivity analyses for missing outcomes. The distinction between the full enrollment and the endpoint population should therefore remain visible when interpreting the estimates.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a model assumes. If a method assumes less variability than the data contain, its standard errors can be too small and its confidence intervals too narrow. This concern is most relevant to models for clustered, repeated, or count data; a simple binary endpoint comparison does not automatically have over-dispersion. The registry record does not report a model-based over-dispersion assessment for this primary analysis.

What is not specified?

The registry record does not report the original sample-size justification, a complete statistical analysis plan, interim analyses, prespecified stratification factors, or details of missing-data sensitivity analyses. The reported results identify the endpoint, its population, the confidence interval method for arm percentages, and the named between-group method. They do not supply enough detail to infer additional design or analysis decisions.

11. Confidence Intervals and Precision

The primary arm-level estimates are 19.8% for rimegepant 75 mg, with a 95% confidence interval from 16.9% to 23.1%, and 10.7% for placebo, with a 95% confidence interval from 8.5% to 13.3%. These intervals describe the precision of each arm’s estimated percentage. The between-group interval is more directly relevant to the treatment contrast: the registry reports a risk difference of 9.2 percentage points, with a 95% confidence interval from 5.4 to 13.0 percentage points.

The interval does not establish the exact value of the difference. It indicates a range of estimates compatible with the data and method, and the span reflects sampling uncertainty. The lower and upper limits are both above zero, so the reported interval is inconsistent with a zero difference at the corresponding confidence level under the analysis assumptions. The interval still includes a range of possible magnitudes, and its limits should be considered along with the point estimate.

The posted unadjusted recalculation gives a risk difference of 9.14 percentage points, with a 95% confidence interval from 5.32 to 12.96 percentage points. This is a simple comparison of the posted summaries, not a replacement for the sponsor’s reported Cochran-Mantel-Haenszel result. The sponsor’s result takes precedence. Small differences between the estimates and interval limits are consistent with the use of different analysis approaches and rounding of arm-level percentages.

Confidence intervals do not capture every source of uncertainty. They do not account for unreported analysis choices, multiplicity, missing-data assumptions, or how well the trial population represents other populations. The registry record does not report enough information to quantify those additional uncertainties.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrative calculations from observed effects, not the trial’s original design assumptions. For the binary endpoints discussed, the figures are participants per arm. The planning assumptions listed are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. The trial’s own sample-size justification and original assumptions are not reported in the registry record.

The 80% power column describes the planned number of participants per arm for a hypothetical future study to have an 80% chance of detecting the selected effect, if that effect and the calculation assumptions hold. The 90% power column describes the corresponding planning target for a 90% chance. These are design probabilities under specified assumptions, not probabilities that a result from an already completed study is correct.

The rows for planning at 100%, 75%, and 50% of the observed effect illustrate how the target effect changes the required sample size. Smaller effects are harder to distinguish from random variation, so planning to detect a smaller effect generally requires more participants per arm. The figures are not observed power. They are not a retrospective measure of how likely the completed trial was to find its result, and they should not be read as evidence that the trial was adequately or inadequately designed.

These estimates depend on the observed event rates and the stated planning assumptions. A future study with different event rates, allocation, analysis, or missing-data patterns could require different numbers. The planning illustrations should therefore be understood as conditional scenarios, not a new recommendation or a reconstruction of the sponsor’s design process.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.107; treatment proportion p₁ = 0.198; average p̄ = 0.153.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5084 = 0.9965.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5043 = 0.4244.
4. n = (0.9965 + 0.4244)² / (0.0914)² = 241.8, rounded up to 242 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.106824925816024                          # control proportion
p1 <- 0.198198198198198                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4574362)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 242 (80% power), 324 (90% power)
 75% of observed effect: n per arm = 404 (80% power), 541 (90% power)
 50% of observed effect: n per arm = 848 (80% power), 1,135 (90% power)
power.prop.test: 241.8 
Simulated power at n = 242 per arm: 0.805 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry’s sponsor-reported primary analysis used the Cochran-Mantel-Haenszel method and reported a risk difference of 9.2 percentage points, with a 95% confidence interval from 5.4 to 13.0 percentage points and p < 0.001. The posted unadjusted recalculation from the arm-level summaries gives a risk difference of 9.14 percentage points, a 95% confidence interval from 5.32 to 12.96 percentage points, and p < 0.001.

The results are close, but they are not identical. The recalculation is a simple unadjusted comparison based on the posted summary statistics; it does not reproduce the sponsor’s named method or any possible adjustment details that are not reported. Rounding of displayed percentages can also affect a recalculation from summaries. The sponsor’s own analysis takes precedence when describing the trial’s reported result.

The same distinction applies to the secondary comparisons: recalculated values describe simple unadjusted contrasts, while the registry reports Cochran-Mantel-Haenszel risk differences. Agreement in direction does not make the methods interchangeable. The reported analysis and its stated method should be the main reference for interpreting the trial, while recalculations are useful as transparent checks of the posted summaries.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple endpoints, time points, or statistical comparisons. With more tests, the chance of at least one apparently positive result can increase, even if each test is interpreted using the same nominal significance threshold. Common approaches include adjusting significance thresholds or specifying a hierarchy that controls the order in which outcomes are tested. The registry record does not report whether such an approach was planned or used for the secondary outcomes.

The primary outcome is clearly identified as pain freedom at 2 hours post-dose. The registry reports a Cochran-Mantel-Haenszel risk-difference analysis and its p-value. For secondary outcomes, it lists multiple measures and assessment windows, while the detailed record does not state a multiplicity strategy. The unadjusted secondary p-values should therefore not be treated as if they were necessarily adjusted for the full set of outcomes and time points.

The primary analysis population is defined as modified intent to treat: randomized participants who took study drug, had a moderate or severe migraine at treatment, and had at least one post-treatment efficacy data point. This definition excludes some randomized participants by design. The primary arm denominators are 666 and 674. The registry does not report a complete participant flow or all reasons that an enrolled or randomized participant might not contribute to the endpoint analysis.

Missing-data handling is a separate concern. The record does not report how a missing 2-hour pain score was handled, whether any imputation was used, or whether sensitivity analyses tested alternative assumptions. Having at least one post-treatment efficacy data point is an inclusion criterion, but it does not specify how missingness at the primary assessment was addressed. The missingness mechanism and its possible effect on the estimate cannot be assessed from the registry information alone.

The registry also does not report the full statistical analysis plan, interim analyses, or the original sample-size justification. Those details should not be inferred from the completed results. These omissions limit assessment of whether all analysis decisions followed a prespecified plan, but they do not alter the numerical results that the registry reports.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infection (0.1%), haemoperitoneum (0.1%), decreased embryo viability (0.1%), ectopic pregnancy (0.1%).

The serious adverse event counts were 1 among 668 participants at risk in the rimegepant 75 mg arm and 2 among 674 participants at risk in the placebo arm. The registry reports zero deaths in each arm. These are counts and denominators, not a complete account of the type, timing, duration, or clinical course of every event.

The listed serious adverse event terms include Infection, Haemoperitoneum, Decreased embryo viability, and Ectopic pregnancy, each reported as 0.1%. The record does not provide further detail in the information about the circumstances or relatedness of these events. The percentages should be read as registry-reported values rather than as evidence about causation.

Other adverse events were recorded for 92 of 668 participants at risk in the rimegepant arm and 94 of 674 in the placebo arm. Those figures are distinct from the serious adverse event counts. The registry data do not, on their own, establish whether a difference in counts is meaningful, or whether every event was attributable to study treatment. Safety interpretation also depends on definitions, follow-up, event collection, and participant-level context not fully described in the record.

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

The primary result shows that, in the modified intent-to-treat population, the recorded percentage with pain freedom at 2 hours was 19.8% with rimegepant 75 mg and 10.7% with placebo. The registry’s reported risk-difference estimate is 9.2 percentage points, with a 95% confidence interval from 5.4 to 13.0 percentage points. This is a comparison of group percentages at a defined assessment time and under the registry’s stated endpoint definition.

The result does not mean that every participant in the active-treatment arm had pain freedom, or that an individual participant’s response can be predicted from the group average. It does not describe the full course of migraine symptoms, later outcomes beyond those assessed, or outcomes that were not part of the registry record. A fixed-time binary result also does not show the distribution of pain scores among participants who did not meet the endpoint.

The trial was conducted in Chinese and Korean patients, and the analysis population had specific eligibility requirements. The result should not automatically be generalized to other populations, care settings, or use patterns. The registry does not report enough detail to assess all features of participant selection, adherence, missing-data handling, or prespecified analysis choices.

The reported p-value is evidence against a zero difference under the specified analysis assumptions, not a measure of treatment importance or a probability that the result is true. The confidence interval communicates uncertainty in the estimated contrast, but it does not account for every possible source of bias or uncertainty. Secondary outcomes and safety counts add context, but they have their own definitions and limitations. Taken together, the posted results describe what was observed in this trial; they do not provide individualized medical guidance or settle questions beyond the measured outcomes and study population.

18. Why This Trial Matters Statistically

This trial is statistically informative because it compares a clearly defined binary endpoint between randomized groups and reports both arm-level estimates and a between-group confidence interval. The pain-freedom threshold is explicit: no pain on the stated scale at 2 hours post-dose. That definition makes it possible to understand what event the percentages represent and to distinguish the endpoint from broader ideas such as overall symptom improvement.

The risk difference communicates the contrast in percentage points, while the confidence interval shows the uncertainty around that contrast. Considering both is more informative than relying on a p-value alone. The registry also identifies the reported method for the between-group analysis, allowing readers to distinguish it from a simple unadjusted recalculation of the arm summaries.

At the same time, the record illustrates why statistical interpretation requires more than a nominally significant primary result. The analysis population is modified intent to treat, secondary endpoints span multiple measures and time points, and the registry does not report the multiplicity strategy or detailed handling of missing endpoint data. These features affect how much weight can be placed on secondary findings and how completely the analysis can be assessed.

The planning illustrations also highlight the difference between prospective design calculations and retrospective power claims. They show how hypothetical sample requirements change with the effect selected for planning, but they do not reproduce the trial’s original rationale. Overall, the study provides a defined comparison with a reported estimate and interval, while leaving important details of the original design and analysis plan unreported.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several limitations arise from the level of detail available in the registry record. The primary efficacy analysis uses a modified intent-to-treat population with specific inclusion criteria, rather than all enrolled participants. The record does not provide a complete flow of participants through screening, randomization, treatment, and analysis, so exclusions and their reasons cannot be fully assessed.

The registry does not report how missing values at the 2-hour primary assessment were handled, whether imputation was used, or whether sensitivity analyses assessed alternative missing-data assumptions. The analysis population requires at least one post-treatment efficacy data point, but that condition does not explain how participants with an unavailable primary assessment were treated. The potential effect of missingness cannot be determined from the reported information.

The record identifies the Cochran-Mantel-Haenszel method for the reported risk-difference analyses, but does not report the stratification factors or other adjustment details. It also does not report the full statistical analysis plan, the sample-size justification, interim analyses, or a multiplicity procedure for the many secondary outcomes and time points. These gaps limit assessment of prespecification and the evidential weight of secondary findings.

The trial summary describes Chinese and Korean patients, but detailed characteristics needed to assess representativeness are not included in the registry record. The registry record also does not provide event-level safety context, such as timing, duration, or relatedness for the listed serious adverse events. These limitations concern interpretation of the available record; they do not change the reported percentages or counts.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety and Efficacy Trial of BHV3000 (Rimegepant) 75 mg for the Acute Treatment of Migraine — NCT04574362.
• Registry record last updated 2023-12-14; status last verified 2023-03.
• Results first posted 2023-12-14.
• 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.

23. Record Summary

The completed Phase 3 study randomized participants to rimegepant 75 mg or matching placebo and used a quadruple-masked, parallel-group design. The registry lists enrollment of 1648 and describes the trial as assessing acute migraine treatment in Chinese and Korean patients.

The primary endpoint was pain freedom at 2 hours post-dose in a modified intent-to-treat population. The registry reports percentages of 19.8% for rimegepant and 10.7% for placebo, with a sponsor-reported risk difference of 9.2 percentage points and a 95% confidence interval from 5.4 to 13.0 percentage points. The reported p-value is p < 0.001.

Secondary outcomes address related measures of pain, function, rescue medication, and symptom timing. The registry also reports serious and other adverse event counts. Multiplicity procedures, detailed missing-data handling, the original sample-size justification, and several elements of the full statistical plan are not reported in the registry record.