This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Comparison of a Drug and Placebo in the Prevention of Migraine Headaches (NCT01122381), a randomized phase 1, phase 2 study. The primary outcome is Migraine Headache Days Per 4 Week Period Comparing the Last 4 Weeks of Treatment to a 4 Week Pre-treatment Baseline..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01122381 |
| Phase | Phase 1, Phase 2 |
| Condition | Headache, Migraine |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | US Department of Veterans Affairs |
| Results posted | Yes |
2. Clinical Question
Population
Veterans with episodic migraine were the population described in the study purpose. The registry record lists headache, migraine as the condition and records enrollment of 5 participants. Further eligibility criteria and participant characteristics are not reported in the registry record.
Intervention
The active intervention was ethosuximide, also described as ESX, in blinded capsules. The arm description specifies 250mg capsules and titration, with a stated expected schedule and possible adjustment for efficacy or tolerability. The record notes that the single subject assigned to study drug did not actually take it according to a subsequent review of ESX drug levels.
Comparator
The comparator was placebo, using blinded capsules described as the same size as the 250mg ESX capsules and a similar titration approach. Further details about how the placebo was prepared or whether participants adhered to the titration are not reported in the registry record.
Primary question
The planned comparison concerned the number of migraine headache days in the last 4 weeks of treatment versus a 4-week pre-treatment baseline, comparing the ESX and placebo groups. The registry record states that the study terminated early and that no outcome data are available, so it does not answer whether the groups differed on this endpoint.
3. Trial Design
The registry describes a randomized, quadruple-masked, parallel-group study in Phase 1 and Phase 2. The listed interventions were ethosuximide and a placebo comparator. Random allocation means the design intended to assign participants to treatment groups by chance; the registry does not report the sequence-generation method, allocation concealment details, or any implementation procedures. Those details are not reported in the registry record.
Quadruple masking indicates that the record classifies the study as masked at four levels, but it does not identify which roles were masked or describe how masking was maintained. The parallel model means the listed groups were intended to receive their assigned intervention rather than cross over between interventions. Further procedural details are not reported in the registry record.
The ethosuximide arm description specifies blinded 250mg ESX capsules, with titration up to 4 capsules qd expected, or 5 or 6 capsules for efficacy, not to exceed the stated “30mg”/kg/d limit, versus maximum tolerability. The placebo description specifies same-size blinded capsules and a similar titration approach. These are descriptions of the planned regimen, not evidence that participants followed it. The record specifically notes that the single subject assigned to study drug did not actually take it according to a subsequent review of ESX drug levels.
Enrollment is recorded as 5. The study status is terminated; the recorded start is 2011-12 and primary completion is 2014-04. The sponsor is the US Department of Veterans Affairs. The reason for termination and the participant flow through the study are not reported in the registry record. The listed dates and status do not establish when or why recruitment or treatment stopped.
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: 5 consented. Initial 4 week baseline period uses headache diary to confirm headache days prior to randomization. 3/5 enrollees did not begin baseline phase; 1 lost to f/u, 1 dis-enrolled due to study interruption, 1 dis-enrolled shortly after consent when another physician began a study excluded drug. 2 enrollees did complete baseline phase.
Overall Study
| Stage | Arm 1-drug Treatment | Arm 2-placebo |
|---|---|---|
| STARTED | 1 | 1 |
| COMPLETED | 1 | 0 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Arm 1-drug Treatment | Arm 2-placebo |
|---|---|---|
| study terminated early | 0 | 1 |
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: Enrollees who completed baseline period and randomization.
| Characteristic | Unit | Arm 1 | Arm 2 | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 1 | 2 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 1 | 2 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 1 | 0 | 1 |
| Sex: Female, Male: Male | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 | 1 | 2 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Migraine Headache Days Per 4 Week Period Comparing the Last 4 Weeks of Treatment to a 4 Week Pre-treatment Baseline., measured over 4 weeks, end of treatment and pre-treatment baseline.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was migraine headache days per 4-week period, comparing the last 4 weeks of treatment with a 4-week pre-treatment baseline. The description says to compare the number of migraine headache days before and after treatment between the ESX and placebo groups. It therefore focuses on change over time within the treatment period and comparison between assigned groups. The registry does not give an outcome value or an exact statistical definition of the group contrast.
General: Counting headache days can express symptom frequency over a defined time window. A baseline period gives a reference for describing what happens during treatment, while a comparison between randomized groups can help separate changes associated with treatment assignment from changes that might occur over time in either group. The usefulness of that comparison depends on complete, consistently measured outcome data and an analysis appropriate to the endpoint.
The registry record states that the study terminated early and that no outcome data are available. It therefore provides the intended measure but no observed endpoint values, group summaries, treatment contrast, or uncertainty estimate. Details such as how headache days were recorded, how missing diary entries were handled, and whether the endpoint was analyzed as a change score or another measure are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the registry record contains no primary outcome data. Although the endpoint and comparison were specified, there is no posted result for migraine headache days. Consequently, there is no estimated difference between ethosuximide and placebo, no confidence interval, and no reported hypothesis-test result for the primary question. The record cannot establish the direction, size, or precision of a treatment-group contrast.
The study enrolled 5 participants and was terminated. The registry also states that the single subject assigned to study drug did not actually take it according to a subsequent review of ESX drug levels. That detail is important when considering exposure, but it does not supply an outcome or permit an estimate of the effect of taking ethosuximide. The record does not report the treatment exposure of the other participants, their endpoint observations, or the reason for termination.
General: An estimate describes the observed contrast, while a confidence interval describes the range of values compatible with the data under the chosen statistical model and its assumptions. Neither can be interpreted when the endpoint observations and analysis results are absent. A small enrollment may make estimates imprecise when results are available, but enrollment alone does not reveal the effect or its uncertainty. It is not a substitute for the missing endpoint data.
No primary analysis is listed, and the registry records 0 analyses. The single primary outcome entry includes a note that the trial ended early without outcome data. The record's note that the primary outcome has several categories or time points and was not reduced to one comparison also means the posted information does not define a single result suitable for interpreting as a treatment contrast. The exact categories or time points behind that note are not reported in the registry record.
The adverse-event figures are separate from the primary efficacy endpoint. They record serious adverse events affecting 0 of 1 at risk in each arm and other adverse events affecting 1 of 1 at risk in each arm. These counts do not provide evidence about migraine-day outcomes, and they do not identify the types of events or establish their cause. Death counts are not reported in the registry record.
In short, the posted information describes a trial design, a planned endpoint, a termination, a drug-exposure note, and limited adverse-event counts. It does not provide a clinical outcome comparison. No conclusion about the relative effects of the interventions can be drawn from the absent primary results.
9. Statistical Methods Explained
What does randomization contribute?
General: Randomization assigns participants to study groups by chance. When carried out as intended, it can reduce systematic differences between groups at the start of a study, including differences that investigators did not measure. It does not guarantee that every characteristic will be balanced, especially in a small study, and it does not correct for missing outcomes or differences in actual treatment exposure. The registry classifies this trial as randomized but does not report the allocation procedure or baseline characteristics.
The parallel design indicates that each participant was intended to remain in an assigned group. A comparison by assigned group is often described as an intention-to-treat comparison, but the registry does not report an analysis population or say that such an analysis was performed. It would be inappropriate to infer a specific analysis approach from the design label alone.
What does masking mean for interpretation?
General: Masking can reduce the influence of knowledge about treatment assignment on participant reporting, treatment decisions, and outcome assessment. The registry labels the study quadruple-masked, but it does not identify the masked roles or report whether masking was maintained. Because the endpoint concerns headache days, the way symptoms were recorded and assessed could matter; those procedures are not reported in the registry record.
How would the endpoint be analyzed?
General: A count of days may be analyzed with methods suited to count outcomes, or as a change from baseline, depending on the protocol and data structure. The modeling choice affects how the estimate and its uncertainty are defined. Count data can show over-dispersion when their variability exceeds what a simple count model expects; methods that accommodate over-dispersion may then be relevant. These are general statistical considerations, not methods identified as used in this trial.
The registry describes a comparison of migraine headache days before and after treatment between the ESX and placebo groups, but does not report an analysis model, estimand, covariate adjustment, handling of baseline values, or calculation of standard errors. It also does not report whether the analysis would compare end-of-treatment values, within-person changes, or another summary. Because no endpoint data are posted, none of these approaches can be evaluated against the observed results.
What can significance tests and intervals tell readers?
General: A significance test evaluates how compatible data are with a specified null hypothesis under a statistical model. A p-value is not the probability that the null hypothesis is true, and it does not measure the clinical importance of an effect. A confidence interval communicates uncertainty around an estimate and can show which effect sizes are compatible with the data and model. Both require an estimate or underlying observations. The registry reports no primary endpoint estimate, confidence interval, or p-value, so there is no inferential result to interpret.
Are there reported sample-size calculations?
The registry describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The assumed effect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence about the trial's original design or its own sample-size justification. The numerical effect fractions and participant estimates are not reported in the registry record. With no posted primary outcome result, these assumptions cannot be used to interpret a trial effect. Any sample-size figure used for planning is an illustration, not observed power.
What analysis plan is documented?
The registry records 0 analyses and does not report a statistical analysis plan, interim analyses, adjustment for multiple comparisons, or a prespecified model. The endpoint description alone does not supply those details. General: A transparent analysis plan helps readers distinguish planned primary analyses from exploratory choices made after data are observed. Without the plan and outcome results, it is not possible to assess model fit, multiplicity handling, or whether reported analyses followed prespecified methods. No such assessment can be made for this record.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome description refers to migraine headache days over treatment and pre-treatment periods, and the registry's skip note says the primary outcome has several categories or time points and was not reduced to one comparison. The registry does not identify the categories or time points represented by that note. It therefore does not provide a single posted primary comparison or a set of results from which multiplicity can be assessed.
The registry does not report whether multiple outcomes, time points, or subgroup analyses were planned, nor whether any adjustment for multiple testing was prespecified. These details are not reported in the registry record. General: When several statistical tests are conducted, the chance of at least one apparently notable result can increase. Prespecified outcome hierarchies or multiplicity adjustments are ways of addressing that issue, but there is no basis for saying which approach was used in this study.
Outcome missingness is consequential because the registry states that no primary outcome data are available. The record does not describe whether measurements were collected and lost, whether participants discontinued before outcome assessment, or how missing values would have been handled. Those details are not reported in the registry record. No imputation method or sensitivity analysis is listed.
The enrollment figure is 5, but the record does not give a participant disposition account or define an analysis population. It notes that the single subject assigned to study drug did not actually take it according to subsequent drug-level review. This is relevant to exposure, but does not identify the population included in an analysis. An intention-to-treat, per-protocol, or safety population is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm 1- Ethosuximide | 0 | 1 | 0.0% |
| Arm 2- Placebo Comparator | 0 | 1 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm 1- Ethosuximide | 1 of 1 |
| Arm 2- Placebo Comparator | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm 1- Ethosuximide | Arm 2- Placebo Comparator |
|---|---|---|---|
| hiccups | Respiratory, thoracic and mediastinal disorders | 1 of 1 | 1 of 1 |
| fatigue | General disorders | 1 of 1 | 1 of 1 |
| diarrhea | Gastrointestinal disorders | 0 of 1 | 1 of 1 |
| abdominal pain | Gastrointestinal disorders | 1 of 1 | 0 of 1 |
| somnolence | Nervous system disorders | 1 of 1 | 0 of 1 |
| nausea | Gastrointestinal disorders | 0 of 1 | 1 of 1 |
The serious adverse-event figures list 1 participant at risk and 0 participants affected in the ethosuximide arm, and 1 participant at risk and 0 affected in the placebo arm. These are the registry's arm-level counts. They do not establish that the interventions have equal safety, particularly because the record has limited enrollment and provides no event descriptions or uncertainty estimates.
For other adverse events, the record lists 1 participant at risk and 1 affected in each arm. It does not identify the event terms, severity, timing, or whether events were considered related to study treatment. These details are not reported in the registry record. The counts refer to participants affected as recorded, not necessarily to the total number of event episodes.
Death counts are not reported in the registry record. The adverse-event entries should be read separately from the primary endpoint: they do not provide migraine-day results and cannot answer the trial's efficacy question. General: Safety counts describe observed events within the recorded follow-up and population. Their interpretation depends on exposure, follow-up duration, event definitions, and completeness of reporting; those details are not available in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, quadruple-masked, parallel-group study of ethosuximide versus placebo was registered for prevention of episodic migraine among veterans. It records enrollment of 5 and a terminated status. It also specifies a planned comparison based on migraine headache days during the last 4 weeks of treatment and a 4-week pre-treatment baseline. These are descriptions of the study and its intended question, not findings about the interventions.
The record does not provide primary outcome observations or an analysis result. It therefore cannot show whether headache-day counts were higher, lower, or similar in either group, and it cannot quantify a difference or its precision. The absence of results is not evidence that there was no effect; it means the registry record does not contain the data needed to estimate one.
The note that the single subject assigned to study drug did not actually take it according to later review of drug levels further limits what can be inferred about exposure. It does not reveal the outcomes of that subject or other participants, and it does not allow an estimate for adherent participants. The reason for trial termination and the degree of follow-up are not reported in the registry record.
The adverse-event counts document limited recorded safety information, but they do not identify the events or establish whether an event was caused by an intervention. They also cannot replace a complete safety assessment. General: Trial interpretation depends on distinguishing assignment from actual exposure, observed outcomes from planned outcomes, and estimates from uncertainty. In this record, the planned comparison is clear enough to identify the question, but the absent endpoint results prevent a statistical answer.
Accordingly, the result is not a positive or negative estimate of treatment effect. It is an incomplete outcome record for a terminated study. Any broader claim about ethosuximide or migraine prevention would go beyond what the posted information supports.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between a registered endpoint and an analyzable result. A registry can describe a carefully framed question and an intended comparison, yet still contain no evidence with which to estimate that comparison. Here, the primary outcome is named, but the record explicitly says that the trial terminated early and no outcome data are available.
The exposure note is also important to interpretation. Assignment to a drug group does not establish that the assigned participant took the intervention. When outcome results are available, analysts may need to distinguish the effect of assignment from the effect of actual exposure, while avoiding post hoc comparisons that undermine the protection of randomization. In this record, no outcome analysis is available to make either comparison.
The enrolled sample and the sparse adverse-event counts also illustrate why counts alone should not be mistaken for precise evidence. General: Estimates from limited data can be uncertain, and event counts do not reveal the range of plausible underlying risks without an appropriate analysis and adequate follow-up. The registry does not provide uncertainty measures or event details that would support such an assessment.
Finally, the record does not document the statistical analysis plan, sample-size justification, missing-data strategy, or multiplicity approach. Those absences limit reproducibility and interpretation, but they should not be filled with assumptions. The record supports a clear account of what was intended and what is unavailable; it does not support a treatment-effect conclusion.
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 most consequential limitation is the absence of primary outcome data. The registry states that the study terminated early and that no outcome data are available. As a result, no effect estimate, confidence interval, or primary test can be interpreted. The primary endpoint description does not establish the actual measurement or analysis procedures used.
Enrollment is recorded as 5, and the record notes that the single subject assigned to study drug did not take it according to later drug-level review. This raises an exposure concern, but participant-level treatment adherence and follow-up are not reported in the registry record. Participant disposition, baseline characteristics, and the analysis population are also not reported in the registry record.
The reason for termination is not reported in the registry record. Nor are the statistical analysis plan, the sample-size justification, the randomization procedure, or the roles covered by quadruple masking. The registry's note about several outcome categories or time points does not identify those categories or provide a single comparison. Missing-data procedures, multiplicity methods, and interim analyses are not reported in the registry record.
Safety interpretation is limited by the small recorded at-risk counts, absent event terms, and missing death counts. Follow-up duration for adverse events and attribution to treatment are not reported in the registry record. These limitations mean the posted safety counts should not be treated as a comprehensive comparison of harms.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Comparison of a Drug and Placebo in the Prevention of Migraine Headaches — NCT01122381.
- Registry record last updated 2015-08-19; status last verified 2015-08.
- Results first posted 2015-08-19.
- 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.
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18. Record Summary
The registry describes a randomized, quadruple-masked, parallel-group Phase 1 and Phase 2 study comparing ethosuximide with placebo for episodic migraine prevention among veterans. Enrollment is recorded as 5, the status is terminated, and the sponsor is the US Department of Veterans Affairs. The recorded start is 2011-12 and primary completion is 2014-04.
The planned primary endpoint compared migraine headache days during the last 4 weeks of treatment with a 4-week pre-treatment baseline between the ESX and placebo groups. The record states that the study terminated early and no outcome data are available. It also notes that the single subject assigned to study drug did not actually take it according to subsequent review of ESX drug levels.
Serious adverse events affected 0 of 1 at risk in each arm; other adverse events affected 1 of 1 at risk in each arm. Event terms and death counts are not reported in the registry record. No treatment-effect estimate can be interpreted from the posted primary outcome information.