A 24-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A 24-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease (NCT00283933), a na phase 2 study. The primary outcome is Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

In broad terms, the study was intended to evaluate safety, tolerability, and pharmacodynamics of migalastat in Fabry disease. It also lists α-Galactosidase A activity in peripheral blood mononuclear cells at baseline, Week 24, and Week 48 as a secondary outcome. The record does not provide results for that measure. With one group and a small enrollment, the study can describe observations among treated participants, but it cannot establish how those observations compare with what would have occurred under a different treatment or no treatment.

3. Trial Design

This was a Phase 2, open-label, single-group study of migalastat in participants with Fabry disease. The registry reports enrollment of 5, no masking, and no allocation to a comparison group. The study began on 2006-05-09, reached primary completion on 2008-03-12, and is recorded as completed. These dates describe the registry record; they do not provide participant-level follow-up or explain when each person completed treatment.

The arm description specifies oral migalastat 150 milligrams QOD during the 24-week treatment period and then during an optional 24-week extension period. The primary outcome timeframe is Day 1 after dosing through Week 48. The extension was optional, so the record does not establish that every participant received treatment or contributed outcome data through Week 48. Individual duration of exposure and follow-up are not reported in the registry record.

The design is not a randomized comparison: there is no separate control arm, and no treatment allocation is listed. The absence of masking means the study was open-label. This allows the record to describe observations during migalastat exposure, but it does not provide a controlled estimate of a treatment difference. Changes over time could not be separated from other influences using a concurrent comparison in this design.

The registry lists two outcome measures. The primary measure counts participants experiencing one or more severe treatment-emergent adverse events. The listed secondary measure concerns α-Gal A activity in peripheral blood mononuclear cells at baseline, Week 24, and Week 48. Results for the primary outcome and the secondary outcome are not reported in the registry record. The record does not describe a protocol rationale for the enrollment, a sample-size justification, interim analyses, or a detailed statistical plan.

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.

Treatment Period

Extension Period

Analysis population for the primary outcome, as defined in the registry: Safety Population: All participants who received at least 1 dose of study drug.

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: All participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs), measured over Day 1 (after dosing) through Week 48.

The primary endpoint is the number of participants who experienced one or more severe treatment-emergent adverse events, with observation spanning Day 1 after dosing through Week 48. A treatment-emergent adverse event is defined as an event beginning on or after study-drug administration, or a pre-existing condition that worsened on or after the first administration on Day 1. The registry defines a severe adverse event as incapacitating and requiring medical intervention.

This endpoint is used to describe a serious level of tolerability concern during the stated observation period. Counting participants with at least one event gives each participant a single contribution to the count, even if that participant experienced more than one event. The measure is therefore a participant count, not a count of all event episodes. The record does not report the primary endpoint count or an accompanying estimate of uncertainty.

Severe and serious are distinct adverse-event classifications. The primary endpoint uses severity, while the adverse-event summary separately reports serious and other non-serious events. A serious adverse event is not necessarily severe under the primary endpoint definition, and the registry’s serious-event count cannot be substituted for the missing severe-event result. The record directs readers to a separate reported-adverse-events module for summaries of serious and other non-serious events regardless of causality.

As a safety measure, the endpoint describes events observed among participants over a defined period; it does not by itself establish that migalastat caused an event. The registry’s primary outcome description includes treatment-emergent timing, but the reported primary count is not available in this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and results determine what statistical conclusions can be drawn. This study has one treatment group, enrollment of 5, and no listed allocation to a comparator. The registry lists no analyses. The primary endpoint is a participant count, and the available adverse-event counts are also presented as participants affected among those at risk. No inferential estimates, confidence intervals, or p-values for these outcomes are reported in the registry record.

What does a participant count represent?

For a binary event outcome, each person can be classified as having or not having at least one event meeting the outcome definition during the specified period. The registry’s primary measure counts participants with one or more severe treatment-emergent adverse events, rather than counting every event episode. This avoids counting a participant multiple times in the primary participant-level outcome when more than one qualifying event occurs. It also means the count does not describe the total number of events or their pattern over time.

In general, a participant count is easiest to interpret alongside a clearly defined population and observation period. Here, the primary outcome specifies a safety population of participants receiving at least 1 dose and a timeframe from Day 1 after dosing through Week 48. The separate adverse-event listing reports 5 at risk in each category. The registry does not provide the primary severe-event count, so that outcome cannot be reconstructed from the separate serious and non-serious counts.

Why do severe and serious events need separate interpretation?

The primary outcome describes severity using its stated definition: an incapacitating event requiring medical intervention. The adverse-event summary instead separates serious events from other non-serious events. These classifications answer different questions and should not be assumed to overlap completely. For that reason, 0 participants with serious adverse events does not establish that 0 participants had severe treatment-emergent adverse events. Nor does the count of participants with other non-serious adverse events establish the primary outcome result.

In general, adverse-event categories also do not establish causation. “Treatment-emergent” describes timing relative to treatment initiation under the registry definition. It does not alone demonstrate that treatment caused the event. The record says the serious and other non-serious adverse-event summaries are regardless of causality, so those counts should be read as events recorded during the study rather than as events attributed to migalastat.

What can a single-group design estimate?

A single-group study can describe outcomes observed among participants who received the study intervention. Without a concurrent comparison group, it cannot directly estimate a difference between migalastat and another intervention or a no-treatment condition. In general, a control group helps account for background event occurrence and other changes over time. Without one, the registry’s counts should remain descriptive rather than being read as a comparative treatment effect.

Open-label conduct means the study did not use masking. In general, knowledge of treatment assignment can influence reporting, assessment, or care, depending on the outcome and setting. This design feature is relevant when interpreting adverse-event reports, but the registry record does not quantify any such influence. No details about event adjudication or blinded review are reported in the registry record.

How should uncertainty be considered?

A confidence interval is a statistical range expressing uncertainty around an estimate under a stated method and assumptions. In general, intervals can show how imprecise a result may be, particularly when the number of participants or events is small. No confidence interval for the primary endpoint or the posted adverse-event counts is reported in the registry record. The reported counts should therefore not be treated as precise estimates of event frequency beyond the participants observed.

Over-dispersion is a general issue for count data when observed variability exceeds what a simple probability model would expect. It is more relevant to repeated event counts or clustered observations than to a single participant-level yes-or-no outcome. The primary measure is a count of participants who experienced at least one event, not a count of all event episodes. The record does not report a model for event counts, and no additional modeling assumptions should be inferred.

What do the planning illustrations mean?

Any sample-size figures associated with an observed-effect calculation are planning illustrations, not observed power and not evidence that the trial was designed around those values. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with an effect defined as a stated fraction of the observed effect. Those assumptions do not describe this trial’s single-group design. The registry does not report that these were the study’s original design assumptions, and they cannot convert a single-group result into a controlled comparison.

In general, a planning calculation asks how many participants might be needed under particular assumptions to detect a specified effect. It is not a measure of the probability that a treatment works, nor does it establish the precision of the observed results. Because this record has no randomized comparison and the primary outcome result is not reported, the planning framework should be kept separate from interpretation of the posted adverse-event counts.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Migalastat")
n      <- c(5)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Migalastat  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary severe treatment-emergent adverse-event count and a secondary measure of α-Gal A activity in peripheral blood mononuclear cells at baseline, Week 24, and Week 48. The record lists no analyses. It does not report a multiplicity strategy, such as adjustment or a hierarchy for interpreting several outcomes. It is therefore not possible to determine how the study planned to control the chance of a false-positive finding across multiple statistical tests.

Missing-data procedures are not reported in the registry record. The optional 24-week extension creates a potential distinction between participants observed during the initial treatment period and those with follow-up through Week 48, but the record does not state how incomplete follow-up was handled or how many participants contributed data at each time point. No imputation method, censoring approach, or sensitivity analysis is reported.

The primary outcome defines the safety population as participants receiving at least 1 dose. The adverse-event summary lists 5 participants at risk in each category, but the registry does not provide a separate efficacy population or a detailed accounting of analysis populations for the pharmacodynamic measure. It also does not state whether all enrolled participants received treatment or completed each period. These omissions limit assessment of how complete the outcome data were.

In general, multiplicity and missing-data methods affect how estimates and tests should be interpreted. A multiplicity plan can clarify which findings are confirmatory, while transparent missing-data methods help show whether incomplete observations could affect conclusions. Neither plan is reported in the registry record, so no assumptions about these procedures should be attributed to the study.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event summary lists the Migalastat group with 5 participants at risk for serious adverse events and 0 participants affected. It separately lists 5 participants at risk for other non-serious adverse events and 5 participants affected. These are participant counts, not total event counts. The record’s death field does not contain a reported value, so death information is not reported in the registry record.

These figures should not be conflated with the primary endpoint. The primary endpoint asks for participants with one or more severe treatment-emergent adverse events and defines severe as incapacitating and requiring medical intervention. The serious-event count uses a separate category. The serious adverse-event count of 0 therefore cannot be used as the missing severe-event result.

The count of 5 affected by other non-serious adverse events means that each participant listed at risk in that category was recorded as affected. It does not identify event types, number of event episodes, severity within the category, timing, duration, or causality. The registry states that the adverse-event summaries are regardless of causality. Detailed event terms are not reported in the registry record.

In general, adverse-event counts describe observations in the defined study group and timeframe. They do not by themselves establish whether an intervention caused an event or how often an event would occur in another population. Here, no concurrent comparator is available, and no uncertainty interval is reported.

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

The available results establish that the registry recorded adverse events in the migalastat group: 0 of the 5 participants at risk were listed as affected by serious adverse events, while 5 of the 5 at risk were listed as affected by other non-serious adverse events. These figures are descriptive counts. The record does not report the primary count of participants with severe treatment-emergent adverse events, so the stated primary safety question remains unanswered by the results in this record.

The figures do not establish that migalastat caused or prevented any event. The adverse-event summaries are recorded regardless of causality, and a single-group study has no concurrent comparison against which to judge whether observed events differed from background experience. The open-label design also offers no masking for assessment. These are limits on interpretation, not evidence for or against a treatment effect.

The results also do not establish a pharmacodynamic response. Although the registry lists α-Gal A activity in peripheral blood mononuclear cells at baseline, Week 24, and Week 48, values and analyses are not reported in the registry record. The record therefore does not show the direction, size, or precision of any change in that measure.

With enrollment of 5, the counts describe a small group. In general, results from a small group are uncertain as estimates of outcomes in a broader population, especially when no interval estimate is reported. The registry does not give a confidence interval for the event counts or an inferential analysis. The fact that the study is marked completed does not fill in the absent outcome results or provide information about individual completion and follow-up.

Accordingly, the record supports a narrow conclusion: it reports the listed serious and other non-serious adverse-event counts among participants at risk. It does not provide the primary severe-event result, detailed event descriptions, a controlled comparison, or the secondary pharmacodynamic results. Any broader claim about comparative safety, efficacy, or biological response would go beyond the information reported.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its design and its primary outcome require careful separation. The study is a single-group, open-label study with enrollment of 5, while the primary endpoint asks for a participant count over a defined safety period. Those features make the record most suitable for describing observations in the treated group, not for estimating a comparative treatment effect.

The adverse-event summary illustrates why outcome definitions matter. The record reports serious and other non-serious categories, but the primary endpoint concerns severe treatment-emergent events, defined by incapacitation and need for medical intervention. Similar everyday wording does not make these statistical categories interchangeable. Keeping the definitions distinct prevents the serious-event count from being mistaken for the primary outcome.

The record also illustrates that completion status and outcome availability are different. The study is recorded as completed, yet the primary endpoint result and the pharmacodynamic values are not reported in the registry record. Without those results, readers cannot assess the primary question or the listed secondary measure from this record. A completed study status alone does not establish that all planned analyses or outcomes are available.

Finally, this case highlights the role of a comparator and uncertainty reporting. A concurrent control could support a direct group contrast; this design does not include one. Confidence intervals and other analyses could communicate uncertainty, but none are reported. In general, these design and reporting elements help distinguish a descriptive observation from evidence about a treatment difference. The registry entry is therefore best read as a limited account of adverse-event counts rather than as a complete statistical evaluation of safety or pharmacodynamics.

15. 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 important limitation is the absence of the primary endpoint result. Although the outcome is defined as the number of participants with one or more severe treatment-emergent adverse events through Week 48, the registry record does not report that count. The separate adverse-event figures use serious and other non-serious categories, which are not interchangeable with the primary severe-event definition.

The design has no comparison group and is open-label. Consequently, the available counts cannot estimate a difference against another treatment or a no-treatment group, and the record cannot separate observed event occurrence from background experience. The absence of masking may also matter for event assessment or reporting in general, but its impact is not quantified.

Enrollment was 5. The record does not report confidence intervals or analyses that would characterize uncertainty around the counts. It also does not provide detailed adverse-event terms, event episode counts, duration, or participant-level follow-up. Death information is not reported in the registry record. The record does not state how many participants completed the initial treatment period or optional extension.

The listed secondary pharmacodynamic outcome lacks reported values and analysis. The registry does not describe missing-data handling, multiplicity methods, a detailed analysis plan, sample-size justification, or interim analyses. These omissions mean that completeness of the outcome data and the planned interpretation cannot be assessed. The planning illustration assumptions are not evidence of the original design or of observed power, and the two-arm assumptions do not match the single-group design.

These limitations are specific to what this registry record reports. They do not establish that additional information is unavailable elsewhere, but such information is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A 24-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease — NCT00283933.
• Registry record last updated 2018-09-07; status last verified 2018-08.
• Results first posted 2018-09-07.
• 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.

19. Record Summary

The registry describes a completed Phase 2, open-label, single-group study of migalastat in Fabry disease, with enrollment of 5. The arm description specifies oral migalastat 150 milligrams QOD during a 24-week treatment period and an optional 24-week extension.

The primary outcome is the number of participants with one or more severe treatment-emergent adverse events from Day 1 after dosing through Week 48. Its result is not reported in the registry record. The adverse-event summary lists 0 of 5 participants affected by serious adverse events and 5 of 5 affected by other non-serious adverse events. Those categories do not replace the primary severe-event result.

A secondary outcome concerns α-Gal A activity in peripheral blood mononuclear cells at baseline, Week 24, and Week 48, but results are not reported in the registry record. No analyses are listed. With no comparator group, the posted counts are descriptive and do not estimate a treatment difference.