Open-Label Phase 3 Long-Term Safety Study of Migalastat: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label Phase 3 Long-Term Safety Study of Migalastat (NCT01458119), a na phase 3 study. The primary outcome is Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

The central statistical question is how to describe adverse events observed during ongoing migalastat exposure in an open-label extension, and how much those observations can establish about treatment-related risk. The study also lists the annualized rate of change in estimated glomerular filtration rate (eGFR) as a secondary outcome. Its result is not reported in the registry record. Because participants entered after completing a previous migalastat monotherapy trial and there is no concurrent comparator, the observations describe the extension-study population rather than a contrast between treatment strategies.

3. Trial Design

This was a Phase 3, open-label extension study of migalastat hydrochloride monotherapy in participants with Fabry disease. Participants had completed treatment in a previous monotherapy trial with migalastat. The study is recorded as a single-group design, with no masking and allocation listed as NA. The registry record identifies Amicus Therapeutics as the sponsor.

The registry record lists an enrollment of 85. The intervention description specifies a 150-mg capsule taken orally QOD. Median duration of exposure was 23.5 m. These details describe exposure in the study; they do not establish that every participant received treatment for the same duration. The study began on 2011-10-14, and primary completion is recorded as 2016-02-17. Its status is TERMINATED.

The primary outcome was the number of participants experiencing TEAEs. The stated observation window ran from baseline to the end of follow-up, described as 30 days after the end of this 42-month study. Adverse-event reporting occurred at study visits, which occurred once every 6 months. The registry record also lists annualized rate of change in eGFR as a secondary outcome. It does not report the statistical plan, the reasons for termination, or results for the primary or secondary efficacy outcomes.

As a single-group, open-label extension, this design can describe events observed during continued treatment among participants who entered the extension. It does not create a concurrent untreated or active-treatment contrast. The registry record identifies the participants as having completed an earlier migalastat monotherapy trial, but details of that earlier trial’s eligibility, treatment course, or relationship to the extension’s analysis are 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.

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 after they enrolled into this open-label extension study.

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: ITT Population: All participants who received at least 1 dose of study drug after they enrolled into this open-label extension study.

6. Primary Endpoint

The registry lists the primary outcome as Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), measured over Baseline to End of Follow-up (30 days after the end of this 42-month study), with AE reporting occurring at each study visit, which occurred once every 6 months..

The primary endpoint counts participants who experienced at least one treatment-emergent adverse event during the specified observation period. A treatment-emergent event was defined as an adverse event beginning on or after the first administration of study drug. An adverse event itself was any untoward medical occurrence in a participant administered migalastat, whether or not it was considered causally related to treatment.

This endpoint is used to describe the frequency of participants who had events during treatment and follow-up. Counting participants differs from counting every event: a participant with multiple events still contributes as a participant experiencing an event. The endpoint therefore summarizes how many participants were affected, not the total number of event episodes, their duration, or their severity distribution. The registry record states that serious and other non-serious adverse events regardless of causality are reported in the Reported Adverse Events module.

The observation period is described as baseline to the end of follow-up, which was 30 days after the end of this 42-month study. Events were reported at study visits occurring once every 6 months. The registry record’s endpoint description identifies the safety population as participants who received at least 1 dose after enrolling in the extension. The primary endpoint result itself is not reported in the registry record, so the event count for this defined endpoint cannot be interpreted from the stated endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation starts by identifying the kind of outcome being measured. The primary endpoint is a count of participants who experienced an event, rather than a continuous measurement such as a laboratory value or a time-to-event outcome. For this kind of endpoint, a participant is counted as having experienced the outcome if at least one qualifying event occurred during the defined observation window. The endpoint does not, by itself, distinguish participants with one event from those with multiple events.

What does the endpoint count?

The registry record defines a TEAE as an adverse event that started on or after the first study drug administration date. It defines an adverse event as an untoward medical occurrence that did not necessarily have a causal relationship with migalastat. This distinction matters: “treatment-emergent” describes when an event began relative to treatment, not whether the treatment caused it. The endpoint is therefore a temporal safety measure, not a direct causal estimate.

The registry record describes serious adverse events using criteria that include life-threatening events, death, persistent or significant incapacitation, inpatient or prolonged hospitalization, and congenital anomaly. Severity was categorized as mild, moderate, or severe based on discomfort and interference with normal everyday activities. These definitions establish how event categories are described; they do not imply that an event’s seriousness or severity establishes its cause.

What does a single-group design allow?

In general, a single-group study can describe what was observed among participants receiving the intervention. Without a concurrent comparator, it cannot directly estimate how the outcome would have differed under another treatment or under no treatment. Differences in participants, follow-up, event detection, or background health can affect observed event counts. An open-label design also means masking was absent, as recorded in the registry; the record does not describe procedures to reduce the influence of that design on event reporting.

The participants came from a prior migalastat monotherapy trial, which makes the extension a selected follow-up population rather than a sample drawn without prior treatment history. The registry record does not report how entry into the earlier trial or completion of its treatment affected selection into the extension. Results from this group should therefore be understood in the context of the stated eligibility history.

How should precision be understood?

In general, a confidence interval describes a range of values compatible with the data under a statistical model and indicates the uncertainty around an estimate. A point estimate alone does not show how precisely an outcome has been estimated. The registry record does not report a confidence interval for the primary endpoint, and it does not report an inferential analysis for that endpoint. Its precision therefore cannot be evaluated from the registry record.

Counts can be useful for describing observed events, but interpretation depends on the definition of the outcome, the number of participants under observation, the duration of their observation, and how complete follow-up was. The record reports enrollment of 85 and median exposure of 23.5 m, but does not provide participant-level observation times or a missing-data analysis. A count should not be treated as a rate over time unless the relevant time-at-risk and method are reported.

What can planning illustrations say?

In general, sample-size planning illustrations estimate how many participants per arm might be needed under specified assumptions to detect a chosen effect with a chosen power. They are design calculations, not observed outcomes, and they are not the same as observed power. The registry record’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a stated fraction of the observed effect. Those assumptions do not turn this single-group extension into a randomized two-arm comparison.

For count outcomes, variability can be more complicated than a simple model assumes. In general, over-dispersion means observed variation is greater than a model’s expected variation; ignoring it can make uncertainty appear smaller than it is. The registry record does not report a model for over-dispersion, a model for repeated events, or any other primary-endpoint analysis method. No analysis method or numerical planning result should be inferred from the stated planning assumptions alone.

What is available for the secondary outcome?

The secondary outcome is annualized rate of change in eGFR. In general, annualizing expresses change relative to time, which can help describe a trajectory when observation duration varies. The registry record does not report the estimated change, its uncertainty, the analysis population used for that outcome, or the model used to estimate it. Consequently, no quantitative interpretation of that secondary outcome is supported by the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures, including the primary TEAE endpoint and the secondary annualized rate of change in eGFR. It does not report whether a multiplicity procedure was used to account for testing more than one outcome, whether outcomes had a prespecified testing order, or how confirmatory and exploratory analyses were distinguished. The statistical plan is not reported in the registry record. Without that information, the role of any outcome testing in a broader inferential framework cannot be assessed.

Missing-data handling is also not reported in the registry record. The endpoint description identifies the safety population as participants who received at least 1 dose after enrolling, but does not explain how incomplete follow-up, missed visits, withdrawals, or missing event information were handled. The record does not state whether all participants in the safety population had complete observation through the end of follow-up.

In general, missing outcome information can affect a safety summary if participants with incomplete follow-up have fewer opportunities for events to be observed. The direction and size of any such effect depend on why data are missing and on the analysis method. No assumptions about missingness or imputation should be attributed to this study because those details are not reported in the registry record.

The registry record also does not report an analysis population for the secondary eGFR outcome or the handling of measurements not available at planned visits. These omissions limit the ability to judge how representative the analyzed information is of the enrolled group. The listed enrollment and the safety-population definition alone do not establish that every outcome was observed for every participant.

11. 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: priapism (3.0%), implantable defibrillator insertion (2.4%), atrial fibrillation (2.4%), pneumonia (2.4%), uterine polyp (1.9%).

The registry record lists 22 participants with serious adverse events and 57 with other non-serious adverse events in the Migalastat group. These are counts of participants, as described in the safety information, and should not be added together: the record does not state whether the categories are mutually exclusive. It also describes adverse events regardless of causality, so the figures do not establish that migalastat caused the events.

The selected serious-event terms and their registry-reported percentages are Priapism, 3.0%; Implantable defibrillator insertion, 2.4%; Atrial fibrillation, 2.4%; Pneumonia, 2.4%; Uterine polyp, 1.9%; and Breast cancer metastatic, 1.2%. They are not a complete listing of all serious events, and the registry record does not provide enough detail to interpret them as comparative risks. The primary TEAE endpoint result is not reported in the registry record.

In general, safety counts should be interpreted alongside the event definitions, observation period, follow-up completeness, and a suitable comparator when the question is whether treatment changes risk. Here, the observation was open-label and single-group, so the figures describe events recorded among participants during the study rather than a treatment-versus-control effect.

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

The study record establishes that an open-label extension followed participants with Fabry disease who had completed treatment in a previous migalastat monotherapy trial. It describes the intervention, the safety endpoint, the observation window, and selected adverse-event counts. These registry entries help define what the study set out to observe and the population in which the observations were made.

The primary endpoint result is not reported in the registry record. The listed serious and other non-serious adverse-event counts provide descriptive safety information, but events were reported regardless of causality. As a result, the counts do not establish that migalastat caused an event, nor do they estimate how event frequency would compare with another treatment or no treatment. The single-group design offers no concurrent control for that comparison.

The registry record also lists annualized rate of change in eGFR as a secondary outcome, but its result is not reported. No conclusion about the observed eGFR trajectory, efficacy, or comparative effectiveness can be drawn from the record’s outcome descriptions alone.

In general, a treatment effect is a contrast between outcomes under different treatment conditions. A single-group observation can characterize what occurred during treatment, but it cannot directly supply the counterfactual outcome that would have occurred without that treatment. The posted information therefore supports a limited descriptive reading: events were recorded during an extension study with the stated regimen and follow-up structure. It does not establish a causal safety effect, a comparative risk, or a clinical benefit.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between documenting events and estimating a treatment effect. Its open-label, single-group structure allows safety observations to be collected during continued migalastat exposure, but it does not supply a concurrent comparison group. That distinction matters whenever event counts are interpreted: observed events are not, by themselves, evidence that treatment caused them or changed their frequency.

The extension also illustrates why endpoint definitions must be read closely. A TEAE is identified by when it begins relative to treatment, while the adverse-event definition explicitly does not require a causal relationship. The primary endpoint counts participants experiencing such events, whereas the listed adverse-event information includes serious and other non-serious events regardless of causality. These descriptions answer related but not identical safety questions.

Exposure duration and observation schedules are also relevant to safety interpretation. The record describes a median exposure of 23.5 m and visits once every 6 months, with follow-up ending 30 days after the end of this 42-month study. These features frame how events were observed, but the registry record does not report individual follow-up time or missing-data handling.

Finally, the record lists a secondary eGFR outcome but does not report its result, and it does not report the primary TEAE result. This demonstrates why a registered outcome definition should not be mistaken for an available result. Careful statistical reading distinguishes the design and intended measurements from the evidence actually reported.

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 main limitation for interpreting this study is its single-group, open-label design. The registry record states that the study was not a randomized comparison and identifies no like-for-like control arm. As a result, observed event counts cannot establish a comparative safety effect or separate treatment effects from other causes of events.

The primary endpoint result is not reported in the registry record, despite a detailed endpoint definition. The secondary eGFR outcome is listed, but its result is also not reported. This prevents quantitative interpretation of either the primary safety outcome or the stated secondary outcome from the registry record.

The study population had completed treatment in a previous migalastat monotherapy trial. The registry record does not report the details needed to assess how selection into that earlier trial, completion of treatment, or entry into the extension might affect the applicability of these observations to other populations. It also does not report participant-level follow-up duration or missing-data handling, so completeness of observation cannot be assessed.

Although the registry describes adverse-event definitions and reporting visits, it does not report the statistical plan, methods for analyzing outcomes, or procedures for handling multiplicity. The listed serious-event terms are selected terms rather than a complete account of all events. These limitations mean the record can describe the design and selected safety counts, but does not support a full assessment of precision, causality, or comparative clinical effects.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open-Label Phase 3 Long-Term Safety Study of Migalastat — NCT01458119.
• Registry record last updated 2018-10-02; status last verified 2018-10.
• Results first posted 2018-10-02.
• 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

NCT01458119 is a Phase 3, open-label, single-group extension study of migalastat hydrochloride monotherapy in participants with Fabry disease who completed treatment in a previous migalastat monotherapy trial. The intervention is described as a 150-mg capsule taken orally QOD, with median exposure of 23.5 m. Enrollment is recorded as 85. The study status is TERMINATED.

The primary endpoint counts participants experiencing TEAEs from baseline through the end of follow-up. Its result is not reported in the registry record. The record lists 22 participants with serious adverse events and 57 with other non-serious adverse events, regardless of causality. It also lists annualized rate of change in eGFR as a secondary outcome, with no result reported in the registry record.

Because the study has no concurrent comparator, the reported safety information is descriptive rather than a comparative estimate of treatment effect. The registry record does not report the statistical plan or missing-data methods.