MLD10 in the Prevention of Migraine in Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MLD10 in the Prevention of Migraine in Adults (NCT02322333), a randomized phase 2, phase 3 study. The primary outcome is Migraine Headache Days.

2. Clinical Question

3. Trial Design

The registry describes a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. It lists the phases as PHASE2 and PHASE3, the status as completed, and the condition as migraine. Pharmalyte Solutions LLC is identified as the sponsor. The recorded study start is 2015-03, and primary completion is recorded as 2017-06. Enrollment is listed as 157.

The brief summary describes screening followed by a 28-day baseline period. During baseline, participants continued their usual migraine treatment and recorded information in a daily headache diary. Participants who continued to meet entry criteria after baseline could enter the treatment phase and be randomized according to a Clinvest-generated schedule. The summary describes an intended allocation of 1:1 between MLD10 and placebo at 6 United States sites, and says approximately 142 participants, 71 per arm, were expected to be randomized into treatment. The enrollment figure and this planned treatment-phase count describe different registry fields; the record does not reconcile them.

The active arm received magnesium L-lactate dehydrate and the comparator received matching placebo. The arm descriptions refer to daily treatment and dispensing at visits, but the dosing instructions in the registry text are incomplete. The record describes serum collection for ionized magnesium, electrolytes, and creatinine, alongside diary assessments. It lists secondary outcomes involving headache days, headache duration, pain severity, acute medication use, migraine disability, and global impressions.

Some design details are not reported in the registry record, including the randomization sequence generation method beyond the reference to a generated schedule, allocation concealment, the full dosing regimen, and the planned statistical analysis. The record’s primary endpoint description identifies an mITT population, but the reported population text is truncated before its total size. These gaps limit how fully the intended design can be reconstructed.

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: The modified intent-to-treat (mITT) population included all randomized subjects who received at least one dose of study drug and obtained at least one endpoint measurement after treating. The mITT population excluded 7 subjects from the MLD10 arm and 6 participants from the Placebo arm. Total mITT analysis population: MLD10 = 73, Placebo = 71.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Migraine Headache Days, measured over Day 1(Screening) - Day 116 (Visit 5 End of Study).

The primary endpoint is the mean change from baseline in the frequency of migraine headache days per 28-day period, comparing MLD10 with placebo at the end of treatment month 3. The stated timeframe runs from Day 1 at screening through Day 116 at the end-of-study visit. The endpoint is continuous: it summarizes headache-day frequency on a scale measured in days, and the registry identifies the mean and standard deviation as the summary statistics.

The registry defines a migraine headache day using diary-relevant clinical criteria. It includes a calendar day with 4 or more hours of migraine headache fulfilling International Classification of Headache Disorders-3beta criteria, and/or a headache of any duration when migraine-specific acute medication is used. The listed medication examples include ergot alkaloids, ergot combinations, opioids, triptans, and combination analgesics of the specified types.

In general, a change-from-baseline endpoint compares a participant’s measurement during treatment with their starting measurement. This can describe whether the outcome shifted over the follow-up period, while comparing arms addresses whether the observed shifts differed between assigned treatments. A 28-day period offers a standardized window for counting headache days, rather than treating a diary period of varying length as directly comparable.

The registry record does not report the arm-specific endpoint means, mean changes, between-arm contrast, confidence interval, or test result. It also indicates that the primary outcome has several categories or time points and is not reduced to one comparison. As a result, the endpoint’s definition is available, but its observed treatment comparison is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

The primary outcome is a continuous measure summarized by a mean. In general, a mean describes the average value across the observations included in an analysis. For a change-from-baseline endpoint, each participant’s follow-up value is considered relative to that participant’s baseline value, and the group mean summarizes those changes. Comparing the group means can address whether the average change differed between assigned arms. The registry identifies the standard deviation as the dispersion measure, but it does not report the observed means or standard deviations for the primary endpoint.

A standard deviation describes how spread out individual observations are around a mean. It is not the same as the uncertainty of the estimated mean or of a between-arm contrast. In general, a confidence interval for an estimate reflects both the spread in the data and the amount of information available. An analysis needs the relevant participant-level data or appropriate summary information to quantify that uncertainty. Neither a confidence interval nor a standard error for the primary comparison is reported in the registry record.

Why compare change between arms?

In a randomized trial, the between-arm comparison is the key contrast for evaluating how outcomes differed under assignment to the study treatments. Looking only at change within the MLD10 arm would not establish how that change compares with what occurred in the placebo arm. The same applies to the placebo arm considered alone. The registry specifies a mean-change comparison, but it does not report the contrast or its uncertainty. Therefore, neither a within-arm description nor a treatment comparison can be reconstructed from the endpoint description alone.

Baseline measurement can help describe where participants began, while change scores describe movement from that starting point. In general, analysis choices can affect precision and interpretation, particularly if baseline values vary or if measurements are missing. The statistical model, any baseline adjustment, and the exact handling of repeated diary measurements are not reported in the registry record. It would be inappropriate to assume a particular model or adjustment strategy.

How should diary counts be understood?

The endpoint counts migraine headache days within a 28-day period. The registry’s definition combines a duration-and-criteria rule with a rule based on use of specified migraine-specific acute medication for headache of any duration. This operational definition determines what qualifies as an endpoint day. For trial interpretation, consistent definitions and diary recording are important because the outcome depends on identifying and classifying days over time.

Diary outcomes can be affected by incomplete recording. In general, missing diary entries are not automatically equivalent to days without migraine. The analysis must specify how incomplete periods are handled, and assumptions about missing observations can affect estimates. The registry record does not report the frequency of missing diary data, the rules for defining evaluable periods, or any imputation or sensitivity analysis. Those omissions leave uncertainty about how the endpoint was derived for participants with incomplete records.

What do the reported population labels establish?

The endpoint description defines the mITT population by randomization, receipt of at least one dose, and obtaining at least one endpoint measurement after treatment began. It says that 7 MLD10 participants and 6 placebo participants were excluded from that population. The mITT total is cut off in the registry description and is not reported in the registry record. Although the trial summary gives an enrollment figure and an approximate planned treatment-phase count, neither should be substituted for the missing endpoint analysis denominator.

In general, analysis populations answer different questions. An intention-to-treat analysis usually seeks to retain randomized participants in their assigned groups, while a treated-and-measured population applies additional eligibility conditions. The precise population definition matters because exclusions after randomization can affect comparability. The registry’s stated mITT criteria are available, but the full participant flow, reasons for exclusions, and the exact analysis set for the reported endpoint are not reported in the registry record. The name of a population alone does not reveal every analysis decision.

What can a planning calculation say?

In general, sample-size planning uses assumptions about the effect to detect, outcome variability, significance level, allocation, and target power. A planning illustration based on an observed effect is not the trial’s original design justification and does not measure the power actually achieved. The stated assumptions for the illustration use a two-sided significance level of 0.05, equal allocation, a normal approximation, and a target effect expressed as a fraction of the observed effect. For non-time-to-event outcomes, such illustrations are defined in participants per arm.

The registry record does not report numerical planning estimates, an observed primary treatment effect, or the variance used for a specific calculation. Further, the primary outcome is flagged as having several categories or time points without a single comparison. Consequently, no numerical planning interpretation can be made from the registry record. Even when a planning estimate is available, it is a hypothetical design illustration, not observed evidence and not a substitute for an estimated effect with its uncertainty.

Why does multiplicity matter?

In general, testing multiple outcomes, time points, or contrasts creates more opportunities for apparently notable results to arise by chance. A statistical plan may identify a primary contrast, organize a testing hierarchy, or adjust inference for multiple comparisons. The registry lists a primary outcome with several categories or time points and indicates that it was not reduced to one comparison. It does not report a multiplicity strategy or identify a selected primary contrast among those categories or time points. Without that information, the inferential status of any individual comparison cannot be established from this record.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint description refers to multiple categories or time points, and the registry record explicitly indicates that the primary outcome has not been reduced to one comparison. It does not identify which category or time point should be treated as the decisive primary comparison, nor does it report a multiplicity procedure. In general, multiplicity matters when several related statistical tests are considered: interpreting each test as if it were the only planned test can overstate the strength of evidence. A prespecified hierarchy or adjustment can address that issue, but the registry record does not describe one.

The available population description is also incomplete. It defines mITT as randomized participants who received at least one dose and obtained at least one endpoint measurement after treatment began. It reports that 7 participants from MLD10 and 6 from placebo were excluded, but the total mITT size is truncated and not reported in the registry record. The record does not provide a full participant flow, reasons for exclusion, arm-specific endpoint denominators, or the number of participants with missing diary measurements.

In general, missing outcome data can affect both the analysis population and the estimate, depending on why data are missing and how the analysis handles them. Methods such as complete-case analysis or imputation rely on different assumptions; none can be attributed to this trial from the registry description. The missing-data strategy, sensitivity analyses, and statistical analysis plan are not reported in the registry record. Accordingly, the influence of missingness and the interpretation of multiple endpoint comparisons remain unresolved.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: osteoarthritis (1.3%), myocardial infarction (1.2%).

The registry lists serious adverse events separately from other adverse events. In the MLD10 group, 1 participant is listed as affected by a serious event among 80 at risk, and 17 are listed as affected by other events among 80 at risk. In the placebo group, 1 participant is listed as affected by a serious event among 77 at risk, and 15 are listed as affected by other events among 77 at risk. Deaths are listed as 0 in each group.

These are descriptive counts, not a complete comparative safety analysis. The at-risk counts shown for the event categories should be retained as the denominators for interpreting those entries; they should not be replaced by the overall enrollment figure. The registry does not report an inferential comparison, confidence intervals, event timing, severity details beyond the serious-event category, or a complete account of causality assessment. The top serious-event terms are listed as Osteoarthritis at 1.3% and Myocardial infarction at 1.2%. The record does not make clear in that listing how those terms map to treatment groups or provide the context needed to interpret them as comparative risks.

In general, adverse-event counts describe events recorded during the study, while a safety conclusion requires attention to definitions, exposure, follow-up, and uncertainty. The listed figures alone do not establish whether a difference between groups is meaningful. They should be read as registry safety entries rather than evidence that either treatment caused or prevented an event.

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

The registry record establishes that the study was designed to compare MLD10 with placebo for prevention of migraine in adults, using change in migraine headache days as its primary endpoint. It describes random assignment, double masking, a parallel design, a baseline diary period, and follow-up through the end-of-study visit. It also provides an operational definition of a migraine headache day and names secondary outcomes. These details clarify the intended research question and measurement approach.

The record does not, however, report the primary between-arm estimate or its uncertainty. It therefore does not establish the observed direction or size of the endpoint difference, how precise that difference was, or how compatible the data were with no difference. No efficacy conclusion should be drawn from the study design, enrollment figure, or endpoint definition alone. The absence of a reported result is not evidence that the treatments were equivalent, nor evidence that one was superior.

In general, statistical evidence is best understood by considering an estimate together with its uncertainty and the analysis choices behind it. A p-value alone, if one were available, would not convey the magnitude or precision of an effect; no primary p-value is reported in any case. For this record, the central efficacy quantities needed for interpretation are absent. The outcome’s multiple categories or time points also remain unresolved, and the registry does not describe multiplicity handling.

The record likewise does not provide enough information to establish the robustness of findings to missing diary data or population definitions. It describes an mITT population but leaves its total size incomplete, and does not report the missing-data approach or sensitivity analyses. Safety counts offer limited descriptive information, but not a complete comparative analysis. Overall, the registry record documents a clinical trial and its planned endpoint, while leaving the primary efficacy result and important inferential details unreported.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why a detailed endpoint definition is not the same as a reported result. The registry specifies a mean change in migraine headache days per 28-day period, gives a diary-based definition of a qualifying day, and identifies the intended comparison between randomized arms. Those elements establish what the investigators sought to measure. Yet the record does not report the mean changes, between-arm estimate, or uncertainty needed to assess the primary comparison.

The distinction matters because readers may otherwise mistake design information for evidence about an effect. Randomization and masking describe features intended to support a fair comparison, but they do not reveal the result. Enrollment and planned allocation describe study size, but they do not identify the actual endpoint analysis population. Similarly, a defined mITT population does not reveal how missing diaries were handled or how many participants contributed to an analysis when its total is not reported.

The multiplicity note is also important. A primary outcome covering several categories or time points needs a clear interpretation strategy, since multiple comparisons can complicate statistical inference. The registry record does not identify a single comparison or describe a multiplicity approach. Without those elements, even a reported isolated result could be difficult to place in context.

For clinical researchers and biostatisticians, the record illustrates the need to distinguish study conduct, outcome measurement, analysis population, and inferential result. Each plays a different role. Here, the registry documents substantial design and measurement detail, but the central efficacy comparison and key analysis decisions are not reported. The appropriate statistical reading is therefore limited: the question and design can be described, but the primary effect cannot be estimated from this record.

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 trial-specific limitation in the registry record is the absence of the primary endpoint comparison. Although the endpoint, unit, summary measure, dispersion measure, and timeframe are described, arm-specific outcome summaries and the between-arm estimate are not reported. A confidence interval and test result are also not reported. This prevents assessment of effect direction, magnitude, and precision.

The registry flags that the primary outcome has several categories or time points and is not reduced to one comparison. It does not clarify which comparison was intended as the principal inferential test or how multiplicity was addressed. The endpoint population description is incomplete: it reports exclusions of 7 participants in MLD10 and 6 in placebo, but the total mITT size is not reported in the registry record. The full participant flow and reasons for those exclusions are also not reported.

Other analysis details are missing, including the statistical model, baseline adjustment, handling of repeated measurements, missing-diary procedures, and sensitivity analyses. The protocol or statistical analysis plan is not described in the registry record, so no assumptions about those choices are warranted. The record gives enrollment as 157 and separately describes an approximate planned treatment-phase count of 142; it does not explain the relationship between those figures.

The safety information is limited to the listed event counts and top serious-event terms. The record does not provide a comparative safety analysis or enough context to interpret those terms by treatment group. The arm dosing descriptions are also truncated, and some methodological details of randomization and masking are not reported. These limitations concern the available registry information; they do not establish what may or may not appear in other study materials.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: MLD10 in the Prevention of Migraine in Adults — NCT02322333.
• Registry record last updated 2020-10-09; status last verified 2020-09.
• Results first posted 2020-10-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT02322333 is a completed, randomized, double-blind, placebo-controlled, parallel-group study of MLD10 for migraine prevention in adults. It is listed as PHASE2 and PHASE3, sponsored by Pharmalyte Solutions LLC, with enrollment of 157. The registry records a study start of 2015-03 and primary completion of 2017-06.

The primary endpoint is mean change from baseline in migraine headache days per 28-day period, comparing MLD10 with placebo at the end of treatment month 3. The registry describes a 28-day baseline diary period and defines which headache days qualify. It also lists secondary outcomes and adverse-event counts.

The primary treatment comparison, its uncertainty, the full mITT size, the missing-data approach, and multiplicity handling are not reported in the registry record. Therefore, the record supports description of the study question and design, but not a statistical conclusion about the primary efficacy result.