Open-label Long-term Safety Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease Who Have Completed a Previous AT1001 Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-label Long-term Safety Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease Who Have Completed a Previous AT1001 Study (NCT00526071), a na phase 2 study. The primary outcome is Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

The study was an open-label extension focused on long-term safety, tolerability and pharmacodynamics. Its population was not described as a new group of participants recruited without prior study participation: the title specifies people who had completed a previous AT1001 study. The primary endpoint counted participants with at least one severe treatment-emergent adverse event, rather than counting the total number of severe events. The registry record does not report the numerical primary-endpoint result, so the frequency of severe treatment-emergent events cannot be described from that endpoint.

The study also listed change in leukocyte α-Gal A activity and migalastat plasma concentration as secondary outcomes. These outcomes address pharmacodynamic and pharmacokinetic questions, respectively, but numerical analysis results for them are not reported in the registry record. With no control group, the study can describe events and measurements observed during treatment in this group; it cannot provide a concurrent comparison of outcomes with and without migalastat.

3. Trial Design

This was a Phase 2, open-label, single-group study sponsored by Amicus Therapeutics. The registry lists 23 participants enrolled, no masking, and allocation as not applicable. The study title and description identify it as an extension for participants with Fabry disease who had completed a previous AT1001 study. The registry lists the start date as 2007-09-17, the primary completion date as 2012-09-08, and the overall status as terminated.

All participants were assigned to the Migalastat group in the posted group-level safety information. The dosing regimen was not a single unchanging schedule across the study: the record describes oral migalastat as 150 mg QOD, 250 mg QD for 3 days, 4 days off per week for 2 months, or 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of protocol amendments at each site. Participants received migalastat for up to 56 months. The record does not give participant-level exposure durations or counts for each regimen.

The primary outcome covered the period from Day 1 after dosing through the end of study, up to 56 months, or follow-up 28 days after the end of study for participants who did not enroll in Study AT1001-041. The safety population was defined as participants who received at least one dose of study drug. No randomized control group is listed. Consequently, the group’s event counts describe safety observations during the study but do not establish how those observations compare with an untreated group or another treatment group. The reason for termination is not reported in the registry record.

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: This study included a dose escalation period (DEP), in which migalastat was administered at 250 milligrams (mg) for 2 months. If there were no safety concerns the dose was increased to 500 mg for up to 10 months, depending on the date of amendment approval. Before and after the DEP, all but 1 participant (post-DEP 300 mg instead) received 150 mg.

Overall Study

Reasons for not completing this 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: 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 EOS (up to 56 months) or follow-up (28 days after EOS).

The primary endpoint was the number of participants who experienced one or more severe treatment-emergent adverse events. A treatment-emergent adverse event was defined as an event that began on or after study-drug administration, or a pre-existing condition that worsened on or after the first administration on Day 1. A severe event was defined as incapacitating and requiring medical intervention.

This endpoint is a participant count: each participant is counted if they experienced at least one qualifying event, regardless of whether they experienced additional severe events. That makes the measure a summary of how many people were affected, rather than a total event count or a measure of event duration. It is a safety endpoint because it focuses on serious impact during treatment exposure and the specified follow-up period. The endpoint’s event-severity definition is distinct from the regulatory seriousness category used in serious adverse-event reporting; serious and severe are not interchangeable terms.

The endpoint’s stated timeframe extended from Day 1 after dosing through the end of study, up to 56 months, or through follow-up 28 days after the end of study for participants who did not enroll in Study AT1001-041. The registry record does not report the observed number of participants who met this primary endpoint. Therefore, its value and the precision of that value cannot be assessed from the posted primary outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s design determines what its statistics can answer. It is recorded as a single-group study, with allocation not applicable and no masking. There is no concurrent control group in the posted design. Its safety summaries can therefore describe events among participants who received migalastat, but they cannot estimate a between-group treatment contrast. The study is open-label, so participants and study staff were not masked to treatment assignment as described in the record.

What does a participant count represent?

The primary endpoint is a count of participants who experienced one or more severe treatment-emergent adverse events. It is not a count of every event. If a participant experienced multiple qualifying events, the endpoint definition still counts that participant once. This kind of binary outcome can be summarized as the number of participants meeting the definition and the number in the relevant analysis population. A proportion can also be informative, but no primary-endpoint count or proportion is reported in the registry record.

The risk window is essential to interpreting such a count. In this study it began after dosing on Day 1 and continued through the end of study, up to 56 months, or through the specified 28-day follow-up for participants who did not enroll in Study AT1001-041. Participants may have had different durations of observation. A simple participant count does not by itself account for differences in time at risk. The registry record does not report a time-to-event analysis for the primary endpoint.

Why distinguish severity from seriousness?

Severity describes the intensity or impact of an event under a specified grading definition. In this endpoint, severe meant incapacitating and requiring medical intervention. Seriousness is a separate classification used for adverse-event reporting. An event can be serious without meeting this study’s severe definition, or severe without necessarily meeting a serious-event criterion. As a result, the 7 participants listed as affected by serious adverse events cannot be used as the missing result for the primary severe-event endpoint.

What can a confidence interval add?

As a general statistical concept, a confidence interval gives a range of values compatible with the observed data under the assumptions of the analysis. It helps communicate how much uncertainty surrounds an estimate; a point estimate alone does not show that uncertainty. For a participant count or proportion, precision depends in part on the number of participants and the number meeting the outcome definition. No confidence interval for the primary endpoint is reported in the registry record, and the primary outcome count itself is not reported, so its precision cannot be evaluated from the posted primary results.

What does the one-group design imply?

Without a concurrent comparison group, there is no randomized estimate of the difference in outcome frequency between treatment groups. Comparing this group with an external population would require information about how comparable the populations, outcome definitions and observation periods were; such a comparison is not reported in the registry record. General statistical adjustment cannot replace a missing control group when the record does not provide the necessary comparison data and assumptions. The design is therefore suited to describing observations in the enrolled group, not to establishing a comparative treatment effect.

How should planning illustrations be understood?

As a general concept, a sample-size calculation expresses how many participants a hypothetical design might require under stated assumptions. The planning illustrations associated with this study are not the trial’s own design justification: they use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, and describe the effect to detect as a fraction of the observed effect. The trial itself is single-group, so those two-arm assumptions do not describe its allocation. Such illustrations are prospective planning aids, not observed power, and they do not change the interpretation of the study’s posted outcomes. The trial’s own sample-size justification is not reported in the registry record.

What analyses are available?

The registry lists three outcome measures, including the primary safety endpoint and the two secondary outcomes. No analysis results are reported in the registry record for these outcomes. In particular, no numeric primary-endpoint result, confidence interval, p-value, or numerical result for the secondary outcomes is available in the posted information. These absences prevent evaluation of statistical precision or formal evidence against a null hypothesis. General methods can explain how such results would ordinarily be interpreted, but they cannot supply the missing estimates.

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(23)
events <- c(9)
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  23  9  39.1  19.7  61.5  22.2  59.2  22.1  59.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary safety outcome and secondary outcomes for change in leukocyte α-Gal A activity through Month 42 and migalastat plasma concentration. It also lists three outcome measures overall. No analysis results are reported in the registry record. A statistical analysis plan, including whether formal hypothesis tests were planned for the secondary outcomes, is not reported in the registry record.

Multiplicity refers, in general, to the increased chance of at least one false-positive finding when several hypotheses are tested. Researchers may address it through prespecified testing sequences, adjusted significance thresholds, or by treating some outcomes as descriptive. Which approach was planned for this study is not reported in the registry record. With no posted inferential results, there is no basis to assess multiplicity adjustment or to interpret a family of p-values.

The primary endpoint result is not reported in the registry record, and numerical results for the secondary outcomes are also not reported. The registry defines the safety population as all participants who received at least one dose of study drug. It does not report the analysis populations used for the secondary outcomes, the amount or pattern of missing data, or methods for handling missing observations. It is therefore not possible to determine whether all enrolled participants contributed to each outcome or how incomplete follow-up affected estimates.

As a general statistical principle, missing-data methods rely on assumptions about why measurements are absent and how that absence relates to outcomes. Different assumptions can lead to different interpretations. The method used in this study, if any, is not reported in the registry record. The study’s termination status is listed, but the reason for termination and any effect on outcome completeness are not reported in the registry record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (8.7%), atrial flutter (4.3%), atrioventricular block (4.3%), cardiac failure congestive (4.3%), ventricular fibrillation (4.3%).

The serious adverse-event summary lists 23 participants at risk and 7 affected in the Migalastat group. The other adverse-event category lists 23 at risk and 23 affected. These are participant-level summaries as recorded for the group; they are not the primary endpoint result. The record’s primary endpoint concerns severe treatment-emergent adverse events, while the serious-event summary uses a different classification.

The listed serious-event terms and percentages are Atrial Fibrillation, 8.7%; Atrial Flutter, 4.3%; Atrioventricular Block, 4.3%; Cardiac Failure Congestive, 4.3%; Ventricular Fibrillation, 4.3%; and Hyperthyroidism, 4.3%. The percentages are reproduced as listed. The record does not report whether participants experienced more than one listed term, so these entries should not be added together or treated as distinct participant counts. It also does not report treatment-relatedness for these terms in the listed information.

The death count is not reported in the registry record. Serious adverse-event counts alone do not show the timing, duration, outcome, or cause of each event. They describe what was recorded for this study group and do not establish a comparative rate in the absence of a control group.

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

The posted record supports a limited descriptive account of safety follow-up in a single group of participants with Fabry disease who had completed a previous AT1001 study. It reports 23 participants enrolled, a safety population defined by receiving at least one dose, and a long-term study period in which participants could receive migalastat for up to 56 months. It also reports serious adverse-event counts and a list of serious-event terms with percentages.

The record does not report the numerical result for the primary endpoint: participants experiencing one or more severe treatment-emergent adverse events. It also does not report numerical results for the secondary outcomes. Thus, the posted information does not allow a reader to quantify the primary endpoint or assess its statistical precision. The serious adverse-event summary is not a substitute because serious and severe are different classifications.

The absence of a concurrent comparator also limits interpretation. The recorded event counts describe the study group, but cannot show what would have occurred in a comparable group receiving another treatment or no study drug. Nor can they separate treatment-associated events from events related to the underlying condition or other factors. The open-label design and dosing-regimen changes are additional context when reading the descriptive findings; the registry does not provide enough participant-level information to examine their effects.

These limitations do not erase the descriptive information that is recorded, but they define what can be concluded from it. The results should not be read as proof for or against a treatment effect, as a controlled risk estimate, or as a complete account of the primary safety endpoint. The reason for study termination, the primary endpoint count, analysis details and missing-data handling are not reported in the registry record. Any stronger interpretation would require information beyond the posted record.

14. Why This Trial Matters Statistically

This study illustrates how trial design and outcome definitions shape statistical interpretation. A long-term extension can collect safety observations during extended exposure in people who completed an earlier study. Here, the registry describes up to 56 months of migalastat exposure and defines a safety population by receipt of at least one dose. Those details establish the setting for the event summaries, but do not turn the study into a controlled comparison.

The primary endpoint also highlights why similar-sounding safety categories must remain distinct. The endpoint counted participants with severe treatment-emergent adverse events under a specific definition. The posted serious adverse-event summary uses a separate category. Treating one as a proxy for the other would answer a different question from the one specified as primary. In this record, the primary count is not reported, so even the most direct descriptive answer to the study’s primary safety question is unavailable.

The study’s single-group, open-label structure matters because observed event counts alone cannot determine comparative risk. A control group can support a direct comparison when the design and analysis are appropriate; no such group is listed. This is especially important when interpreting percentages or event terms as if they were treatment effects. They describe the recorded group and do not quantify a difference attributable to treatment.

Finally, the record shows why completeness of outcome reporting matters alongside enrollment and follow-up information. It lists secondary pharmacodynamic and pharmacokinetic outcomes, but numerical results are not reported. It also does not report the reason for termination or methods for missing data. Statistical interpretation depends not only on a trial’s design, but on having the estimates, denominators and analysis details needed to understand what was observed and how uncertain it is.

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.

This is a single-group, open-label study with no concurrent comparator. Its adverse-event summaries are descriptive and cannot estimate a randomized difference between treatment groups. Participants had completed a previous AT1001 study, so the study population is specifically defined by prior participation; the record does not establish how well the group represents people with Fabry disease more broadly.

The registry does not report the primary endpoint count for severe treatment-emergent adverse events. It also does not report numerical results for the secondary outcomes, confidence intervals, p-values or the analysis methods used. As a result, the precision of the primary safety outcome and the magnitude of any secondary-outcome changes cannot be assessed from the registry record. The serious-event summary does not fill this gap because seriousness is distinct from the primary endpoint’s severity definition.

Dosing could vary with protocol amendments and their approval dates at each site. Although the record gives the described regimens and says participants received migalastat for up to 56 months, it does not report how many participants received each regimen, their individual exposure durations, or outcomes by regimen. It also does not report the reason for termination, participant flow over time, missing-data methods, or whether missingness affected the outcome summaries. These omissions restrict interpretation of exposure and follow-up completeness.

The serious-event listing gives selected terms and percentages but does not provide, in the listed information, participant overlap across terms, event timing, duration, outcomes, or treatment-relatedness. The death count is not reported in the registry record. These limits mean the posted information offers only a partial view of the study’s safety experience.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-label Long-term Safety Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease Who Have Completed a Previous AT1001 Study — NCT00526071.
• Registry record last updated 2018-10-03; status last verified 2018-10.
• Results first posted 2018-10-03.
• 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

NCT00526071 is a Phase 2, open-label, single-group extension study of migalastat in participants with Fabry disease who had completed a previous AT1001 study. The registry lists 23 participants enrolled, a start date of 2007-09-17, a primary completion date of 2012-09-08, and a terminated status. Participants received oral migalastat under regimens that could vary with protocol amendment approval dates at study sites, for up to 56 months.

The primary outcome was the number of participants with one or more severe treatment-emergent adverse events during the specified treatment and follow-up period. Its numerical result is not reported in the registry record. The serious adverse-event summary lists 7 affected among 23 at risk; the other adverse-event category lists 23 affected among 23 at risk. Secondary outcomes concerned leukocyte α-Gal A activity and migalastat plasma concentration, but their numerical results are not reported. The registry does not list a concurrent comparator group, and the reason for termination is not reported in the registry record.