Staccato Prochlorperazine in Migraine (Out Patient): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Staccato Prochlorperazine in Migraine (Out Patient) (NCT00422812), a randomized phase 2 study. The primary outcome is Headache Pain Relief at 2 hr.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, double-blind, placebo-controlled, parallel-group outpatient study of inhaled Staccato prochlorperazine. The registry describes masking as quadruple. Participants were allocated to inhaled placebo or one of three prochlorperazine doses: 5 mg, 7.5 mg, or 10 mg. The study title and official title identify it as a single-dose efficacy and safety study in patients with migraine headache.

The listed enrollment was 400. The recorded start was 2006-04, primary completion was 2007-01, and status is completed. Those registry dates describe the recorded study milestones; they do not establish the duration of follow-up for every participant. The primary endpoint timeframe is 2 hr post-dose. The registry also lists two secondary outcomes, assessed at 2 hours and over 0 to 4 hours.

The primary result uses the ITT w/ LOCF Population. The record does not report the original sample-size justification, the trial’s detailed allocation procedures, the exact operational meaning of quadruple masking, or a full statistical analysis plan. It also does not report the number randomized and analyzed by arm as separate quantities in the primary result. The listed arm counts belong to the endpoint analysis and should not be treated as a substitute for a complete participant-flow account.

The registry’s brief summary describes the study as assessing efficacy and safety in outpatients with migraine headache with or without aura. It also mentions an earlier Phase 2A study, but that earlier study is not the trial analyzed in these results. The current record concerns the Phase 2B study and the placebo-controlled comparisons among its four assigned groups.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: ITT w/ LOCF Population

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: Safety Population

6. Primary Endpoint

The registry lists the primary outcome as Headache Pain Relief at 2 hr, measured over 2 hr post-dose.

The primary endpoint is the number of participants with headache pain relief at 2 hr post-dose. Relief is defined according to the IHS definition as headache pain rated none or mild. The endpoint therefore reduces each participant’s reported pain status at the specified time to a binary outcome: meeting the relief definition or not meeting it. The registry identifies the analysis population as ITT w/ LOCF Population.

A binary endpoint gives a directly interpretable count in each group and can support comparisons of the proportion meeting the stated response definition. The recalculated results express the difference between each prochlorperazine dose group and placebo as a risk difference, with confidence intervals. This helps describe both the direction and the precision of the observed difference. The registry’s own primary analysis is a Cochran-Mantel-Haenszel comparison across the four groups.

A single assessment at 2 hours addresses the endpoint at that recorded time; it does not capture every aspect of the headache experience or establish how long relief lasted. The separate secondary outcomes address pain-free response at 2 hours and the recorded survival of headache pain relief over 0 to 4 hours. Those outcomes use different definitions or time structures and should not be treated as interchangeable with the primary measure. The registry record does not report further details about how pain was measured or how missing endpoint values were handled beyond identifying the population as ITT w/ LOCF.

7. Results Posted in the Registry

• Inhaled PCZ 5 mg: 60.2% (62/103) versus 40.8% (40/98) on control; risk difference 19.4 percentage points (95% CI 5.8 to 32.9), risk ratio 1.47 (1.11–1.96); unadjusted two-proportion z-test p = 0.006.
• Inhaled PCZ 7.5 mg: 63.7% (58/91) versus 40.8% (40/98) on control; risk difference 22.9 percentage points (95% CI 9.1 to 36.8), risk ratio 1.56 (1.18–2.08); unadjusted two-proportion z-test p = 0.002.
• Inhaled PCZ 10 mg: 66.0% (68/103) versus 40.8% (40/98) on control; risk difference 25.2 percentage points (95% CI 11.8 to 38.6), risk ratio 1.62 (1.23–2.13); 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.

Responders, Pain-Free at 2 Hours

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Inhaled PCZ 5 mg: 21.4% (22/103) versus 15.3% (15/98) on control; risk difference 6.1 percentage points (95% CI -4.6 to 16.7), risk ratio 1.40 (0.77–2.53); unadjusted two-proportion z-test p = 0.268.
  • Inhaled PCZ 7.5 mg: 29.7% (27/91) versus 15.3% (15/98) on control; risk difference 14.4 percentage points (95% CI 2.6 to 26.1), risk ratio 1.94 (1.10–3.40); unadjusted two-proportion z-test p = 0.018.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Inhaled PCZ 5 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Inhaled PCZ 7.5 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Survival of Headache Pain Relief

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Inhaled PCZ 5 mg: 73.6% (67/91) versus 74.8% (77/103) on control; risk difference -1.1 percentage points (95% CI -13.5 to 11.2), risk ratio 0.98 (0.83–1.16); unadjusted two-proportion z-test p = 0.857.
  • Inhaled PCZ 7.5 mg: 68.9% (71/103) versus 74.8% (77/103) on control; risk difference -5.8 percentage points (95% CI -18.1 to 6.4), risk ratio 0.92 (0.78–1.09); unadjusted two-proportion z-test p = 0.353.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Inhaled PCZ 5 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Inhaled PCZ 7.5 mg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes offer complementary perspectives on response, but they do not simply replicate the primary endpoint. Pain-free response at 2 hours uses a stricter response state than the primary definition, which includes both none and mild pain. The survival outcome follows headache pain relief over a stated interval and is analyzed with a time-to-event method. The registry results show that the direction and statistical evidence vary across these distinct outcome definitions and analyses; they should not be collapsed into one overall claim.

The reported secondary analyses include both group-level and pairwise tests. For pain-free response, the registry lists Fisher Exact comparisons for placebo against the 5 mg and 7.5 mg groups. For survival of headache pain relief, it lists an overall Log Rank comparison and a placebo-versus-5 mg comparison. The registry does not report a complete set of sponsor analyses for every possible pairwise comparison, and the secondary endpoint results do not have the same reporting structure as the primary result.

Secondary findings generally carry less confirmatory weight when multiple outcomes, groups, or comparisons are examined without a reported multiplicity strategy. A nominal p-value does not account for the number of opportunities to observe an apparently notable result. The registry record does not report whether the secondary analyses were prespecified as confirmatory, how multiplicity was handled, or whether any hierarchy was used. Accordingly, these outcomes can inform the overall pattern and identify questions for further evaluation, but they should be interpreted alongside the primary result and the limits of their analysis and reporting.

The secondary results also differ in how the outcomes are measured and in the statistical tests used. A count at one time point and an event-time analysis convey different information. Neither should be assumed to measure the same aspect of response as the primary endpoint. The posted secondary data are descriptive of this trial and do not independently resolve the limitations around analysis populations, missing data, or multiple testing.

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

• Responders, Pain-Free at 2 Hours
• Survival of Headache Pain Relief

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary: each participant either met the registry’s definition of headache pain relief at 2 hr post-dose or did not. The posted arm values are counts of participants, not averages of a continuous measurement. The recalculated dose-versus-placebo summaries use risk differences. A risk difference compares the event proportions in two groups by subtracting one proportion from the other; a positive estimate means the event was more frequent in the dose group in the observed data. No new risk differences are calculated in this explanation.

What does the registry’s overall test assess?

The registry lists a Cochran-Mantel-Haenszel analysis for the four primary endpoint groups and labels it a superiority analysis. This method is used to test for an association between group and a categorical outcome, with the ability to account for strata when they are part of the analysis. The registry record does not identify any stratification factors or provide the test statistic, effect estimate, or confidence interval. Its reported p-value is 0.001. That overall test should be distinguished from the separately recalculated comparisons of each dose against placebo.

How do the recalculated comparisons differ?

The recalculated comparisons use the posted summary counts for placebo and one dose at a time. They are simple, unadjusted comparisons and include a risk difference, a confidence interval, and an unadjusted p-value. Unadjusted means the reported comparison is not presented as accounting for the set of multiple dose comparisons. These recalculations are not a reconstruction of every detail of the sponsor’s analysis; they use the posted summary statistics.

The confidence interval gives a range of values compatible with the observed data under the calculation method. For a risk difference, an interval that includes zero is compatible with no difference as well as with differences in either direction; an interval that excludes zero is less compatible with no difference under that method. The interval’s width conveys precision: wider intervals represent less precise estimates. These intervals are not adjusted for multiplicity unless explicitly stated, and the registry does not report an adjustment for these recalculations.

Why are other tests listed for secondary outcomes?

The registry reports Fisher Exact tests for comparisons of pain-free response at 2 hours. Fisher’s Exact test evaluates evidence of association in a two-group categorical outcome and is suitable for count data. For survival of headache pain relief over 0 to 4 hours, the registry reports Log Rank analyses. A log-rank test compares event-time patterns between groups over follow-up, rather than comparing only a single endpoint count. The record does not give the event definition and censoring details needed to fully assess the time-to-event analysis.

Different tests can address different data structures and questions. A test p-value measures how compatible the observed data are with a specified null hypothesis under the test’s assumptions; it is not the probability that the null hypothesis is true, nor a measure of the size or clinical importance of an effect. Estimates and confidence intervals are needed to describe magnitude and precision. For the registry’s primary overall test, those quantities are not reported.

What information about the statistical plan is absent?

The registry does not report the original sample-size justification, the planned handling of multiplicity, interim analyses, or a complete statistical analysis plan. It identifies the primary population as ITT w/ LOCF, but does not provide the numbers of participants with missing primary outcome data or the detailed LOCF procedures. Those omissions matter because analysis choices and missing-data patterns can affect interpretation. The posted results support description of the stated analyses, but do not permit a full audit of the prespecified plan or all assumptions behind it.

The planning illustrations use two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. For time-to-event planning, the displays concern total events; for other outcomes, they concern participants per arm. These assumptions belong to the illustrations and should not be confused with unreported assumptions in the trial’s original design.

11. Confidence Intervals and Precision

The recalculated primary risk differences have confidence intervals that exclude zero for all three dose-versus-placebo comparisons. This indicates that, under the unadjusted methods used, the intervals do not include no difference. The intervals nevertheless span a range of possible effects, so the point estimates should not be read as exact values. The 5 mg, 7.5 mg, and 10 mg group comparisons each have uncertainty, and the widths of their intervals reflect the amount of information in the posted counts and the calculation method.

A confidence interval is a measure of statistical precision under its assumptions. If the study and calculation were repeated many times under the same conditions, the interval procedure would capture the target parameter at its stated confidence level in the long run. It does not mean that there is a specified probability that the fixed true effect lies in the one interval observed. The registry record does not report the confidence level for the recalculated intervals as a separate field, so no confidence percentage is asserted.

The pairwise confidence intervals are unadjusted. Considering several comparisons can make the overall chance of at least one misleading positive finding greater than for a single comparison, unless an appropriate multiplicity strategy is used. The registry record does not report whether such a strategy was specified. The sponsor’s overall test supplies a separate group-level result, but it is not an effect estimate and does not show the precision of each pairwise contrast.

Precision also depends on outcome frequency and analyzed group size. Counts and group sizes are reported for the primary endpoint, but the record does not provide a full accounting of missing data or participant flow. That makes it difficult to assess whether the listed analyzed groups fully reflect the randomized groups. Confidence intervals quantify sampling uncertainty under the calculation method; they do not account for every design, measurement, missing-data, or reporting limitation.

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 sample-size illustrations translate an observed effect into planning examples for hypothetical two-arm comparisons. For outcomes other than time-to-event, each displayed number is participants per arm. For the time-to-event outcome, the numbers refer to total events, not participants per arm. The distinction matters: an event target is not the same quantity as an enrollment target, because the number of participants needed to observe a given number of events depends on event occurrence and follow-up.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is a stated fraction of the observed effect. Rows describe planning for 100%, 75%, or 50% of the observed effect. The 80% power column gives the planning number needed per arm, or the total number of events for time-to-event outcomes, for an analysis to have an 80% chance of detecting the specified effect under the assumptions. The 90% column uses a higher chance of detection and therefore generally requires a larger planning quantity.

Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants or events. These numbers are illustrations based on the observed estimates, not the original trial’s design justification. The original sample-size assumptions are not reported in the registry record. This is not observed power: it does not measure the probability that the completed trial detected an effect, and it should not be used to interpret the observed p-values as a retrospective probability of success.

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 = 0.408; treatment proportion p₁ = 0.602; average p̄ = 0.505.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7071 = 1.3858.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6937 = 0.5838.
4. n = (1.3858 + 0.5838)² / (0.1938)² = 103.3, rounded up to 104 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 <- 0.408163265306122                          # control proportion
p1 <- 0.601941747572815                          # 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(422812)
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 = 104 (80% power), 138 (90% power)
 75% of observed effect: n per arm = 185 (80% power), 247 (90% power)
 50% of observed effect: n per arm = 414 (80% power), 554 (90% power)
power.prop.test: 103.3 
Simulated power at n = 104 per arm: 0.791 (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 sponsor’s reported primary analysis is a Cochran-Mantel-Haenszel superiority test across the four groups, with p = 0.001. It is an overall test and the registry does not report its effect estimate or confidence interval. The recalculated results instead compare each active dose with placebo using the posted group counts and provide unadjusted pairwise estimates, intervals, and p-values. The two types of result should not be treated as interchangeable because they answer different statistical questions.

The registry record indicates no discrepancy between the posted summary statistics and the recalculated results. The sponsor’s analysis remains the primary reported analysis; the simple recalculations are supplementary descriptions based on posted counts. For the primary endpoint, each recalculated dose-versus-placebo comparison has a positive risk-difference estimate, and its unadjusted confidence interval excludes zero. Those pairwise findings do not replace the sponsor’s overall test, and they do not establish that the sponsor used the same pairwise method or multiplicity approach.

The registry does not provide details of the full statistical analysis plan, adjustments for multiple comparisons, or additional model specifications. As a result, the sponsor’s reported overall p-value can be cited as reported, but a more complete comparison of prespecified and recalculated methods is not possible from the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The primary registry analysis is an overall comparison across the four randomized groups. The recalculated results also make three dose-versus-placebo comparisons. Considering several hypotheses raises a multiplicity issue: when many comparisons are tested, the chance of seeing at least one apparently strong result by chance can increase. A prespecified adjustment or testing hierarchy can address that issue, but the registry record does not report whether one was planned or applied. The recalculated pairwise p-values are explicitly unadjusted.

The registry reports a primary population labeled ITT w/ LOCF. LOCF means carrying the last recorded observation forward for participants with missing later measurements, but the record does not describe the exact implementation, the number of missing primary outcomes, or the timing and reasons for missingness. It also does not report sensitivity analyses using alternative missing-data assumptions. Without those details, the effect of missing data on the estimated group comparisons cannot be assessed from the registry record.

The registry does not report the original sample-size justification, interim analyses, a complete analysis plan, or a participant-flow account with the numbers randomized, treated, and analyzed at each stage. It does not state how protocol deviations were handled or whether any additional populations were analyzed. These items are important for evaluating whether the posted analyses match the planned analyses and for understanding the consequences of exclusions or missing observations.

The presence of an overall test does not by itself establish how multiplicity was handled for all secondary endpoints or pairwise comparisons. Nor does the record explain whether the secondary analyses were confirmatory or exploratory. These omissions do not erase the recorded results, but they limit the strength of conclusions that can be drawn from the full set of statistical tests.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in each group: the serious-event counts are 0 among 98 participants at risk for placebo, 0 among 104 for 5 mg, 0 among 93 for 7.5 mg, and 0 among 105 for 10 mg. It also reports zero deaths in every group. These are the recorded counts for the listed at-risk group sizes; they do not establish that an event is impossible or rule out uncommon risks.

The record separately lists participants affected by other adverse events: 12 in the placebo group, 67 in the 5 mg group, 67 in the 7.5 mg group, and 91 in the 10 mg group. The registry does not provide the adverse-event terms in the listed serious-event summary, and it does not report enough detail to characterize severity, timing, duration, or causality for the other adverse events. The figures should therefore be read as group counts, not as a complete account of the nature or clinical importance of events.

Different at-risk group sizes appear in the safety results than in some primary endpoint groups. The registry record does not provide the participant-flow details needed to explain these differences. Safety counts alone do not permit a complete comparison of risks, particularly without event descriptions, follow-up information, and detail about how events were collected and classified.

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

The primary result shows that more participants in each prochlorperazine dose group than in the placebo group met the recorded definition of headache pain relief at 2 hours. The unadjusted recalculated estimates favor each dose on this endpoint, with confidence intervals excluding zero. The registry’s reported overall test also reports a group-level superiority result. Together, these findings describe the posted trial results for the specified endpoint and analysis population.

They do not establish the size of benefit with certainty. The pairwise estimates have confidence intervals, the comparisons are unadjusted, and the record does not report how multiplicity was handled. The sponsor’s overall test does not provide an effect estimate or confidence interval. The primary outcome is measured at a particular time and by a defined threshold; it does not establish response at other times, duration beyond the listed follow-up, or effects on outcomes that were not assessed.

The registry record also does not provide the full statistical analysis plan, original sample-size justification, detailed missing-data information, or complete participant flow. These gaps matter when judging how robustly the recorded analyses represent the trial as designed. The secondary outcomes address related but distinct questions, and their analyses should not be treated as interchangeable with the primary endpoint or as independent confirmation without considering multiplicity.

The trial was a randomized, blinded, placebo-controlled Phase 2 study in outpatients with migraine headache, with or without aura. Its findings describe the participants and measurements recorded in this study. They do not by themselves establish broader applicability to other populations or settings, and they are not a substitute for a complete account of safety, follow-up, or all planned analyses. Statistical results describe uncertainty in the data; they do not determine what an individual should do.

18. Why This Trial Matters Statistically

This trial illustrates the difference between an overall multi-group test and a set of pairwise comparisons. The registry reports a Cochran-Mantel-Haenszel result across placebo and three dose groups, while the recalculated comparisons estimate each dose-versus-placebo risk difference separately. Keeping those questions distinct prevents the overall p-value from being mistaken for a dose-specific effect estimate.

It also highlights why effect estimates and confidence intervals matter alongside p-values. The primary endpoint is a count-based binary outcome, so risk differences express the absolute contrast between groups, while intervals describe the uncertainty around those estimates. A p-value alone does not show the magnitude or precision of a contrast. Nor does an interval remove concerns about unadjusted multiple testing or missing observations.

The study’s three dose arms create several plausible comparisons, and the registry does not report a multiplicity strategy. The secondary outcomes add still more analyses with different definitions and statistical methods. That makes transparent reporting of prespecified hypotheses, analysis populations, missing-data procedures, and testing plans important for interpreting the complete set of results.

Finally, planning illustrations based on observed effects can help readers understand how sample-size needs change when the assumed target effect changes. They are not evidence about the design assumptions used when the trial was initiated. The distinction between an illustrative planning calculation and the trial’s original justification is essential to avoid reading retrospective calculations as evidence of observed power or as a reconstruction of the protocol.

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.

The primary endpoint is reported for an ITT w/ LOCF Population, but the registry does not provide the numbers or reasons for missing observations, the detailed LOCF procedure, or sensitivity analyses. This limits assessment of whether missingness could have influenced the endpoint comparisons. A detailed flow of participants from randomization through analysis is also not reported, so the differences among listed endpoint and safety group sizes cannot be fully explained.

The registry gives an overall primary p-value but no associated effect estimate or confidence interval for the Cochran-Mantel-Haenszel analysis. The pairwise comparisons are recalculated from posted summary counts and are unadjusted. The original analysis plan, multiplicity procedures, interim analyses, and original sample-size justification are not reported. Consequently, the relationship between the full prespecified analysis and all posted results cannot be verified from this record.

The outcome definitions and timeframes constrain interpretation. The primary measure is pain relief at 2 hr post-dose, while the secondary outcomes use pain-free response at 2 hours and survival of pain relief over 0 to 4 hours. The registry record does not provide further measurement details or all event-time analysis specifications. These measures do not establish results for other timepoints or outcomes.

The safety results provide serious-event and death counts, but the listed serious-event terms are absent, and the record does not provide detailed descriptions of the other adverse events in the summary. Without fuller information about event types, follow-up, classification, and participant flow, the safety counts cannot characterize the complete safety profile. The results are also specific to the studied outpatient population and trial setting; broader applicability is not established by the registry results alone.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Staccato Prochlorperazine in Migraine (Out Patient) — NCT00422812.
• Registry record last updated 2018-01-25; status last verified 2008-06.
• Results first posted 2018-01-25.
• 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

NCT00422812 is a completed Phase 2 randomized, double-blind, placebo-controlled, parallel-group study of single-dose inhaled Staccato prochlorperazine for outpatients with migraine headache, with or without aura. The four groups received inhaled placebo or prochlorperazine at 5 mg, 7.5 mg, or 10 mg. The primary endpoint was headache pain relief at 2 hr post-dose, defined as none or mild pain, in the ITT w/ LOCF Population.

The registry reports an overall Cochran-Mantel-Haenszel primary analysis and posts group counts that support unadjusted dose-versus-placebo recalculations. The primary endpoint counts are higher in each dose group than in placebo, while the recalculated pairwise intervals exclude zero. Interpretation is limited by unreported multiplicity and missing-data details, absent original design assumptions, and incomplete participant-flow and safety-event detail. Secondary outcomes provide related but distinct measures and should be interpreted with those limitations in mind.