This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Drug-Drug Interaction Study Between AT1001 (Migalastat Hydrochloride) and Agalsidase in Participants With Fabry Disease (NCT01196871), a non-randomized phase 2 study. The primary outcome is Change In Area Under The Plasma Concentration Versus Time Curve (AUC) For Active α-Galactosidase A (α-Gal A) Levels After Administration Of Migalastat.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01196871 |
| Phase | Phase 2 |
| Condition | Fabry Disease |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amicus Therapeutics |
| Results posted | Yes |
2. Clinical Question
The study asked whether migalastat changes the plasma pharmacokinetics of agalsidase, and whether agalsidase changes the safety and pharmacokinetics of migalastat. It enrolled 20 participants with Fabry disease in a non-randomized, open-label, sequential study. The interventions included migalastat hydrochloride at 150 mg or 450 mg and agalsidase beta or agalsidase alfa.
Population
Participants with Fabry disease. The registry reports an enrollment of 20. Pharmacokinetic analyses used participants with evaluable pharmacokinetic parameter data who had successfully completed at least Period 1 and Period 2 in any stage.
Intervention
Migalastat was administered at 150 mg or 450 mg, in study stages that also included agalsidase beta or agalsidase alfa. The registry describes the primary question as the effect of migalastat on agalsidase plasma pharmacokinetics.
Comparator
The record describes sequential periods involving agalsidase alone and co-administration with migalastat. This was not a randomized, like-for-like comparison between independent groups; the allocation was non-randomized and the study was unmasked.
Primary question
How did the area under the plasma concentration-versus-time curve for active α-Gal A change after migalastat administration? The study also aimed to assess the effects of agalsidase on migalastat safety and pharmacokinetics. Numerical primary outcome estimates are not reported in the registry record.
The question is about drug-drug interaction and measured pharmacokinetic behavior, not a clinical outcome comparison. The record describes sampling before and after infusions and at follow-up time points, and specifies that enzyme activity in plasma was measured with a qualified assay. It does not report the numerical primary endpoint results, so the magnitude and direction of any observed change cannot be described from the registry record.
3. Trial Design
This completed Phase 2A study was open-label, non-randomized, and sequential, with an enrollment of 20 participants. It examined drug-drug interactions between migalastat and agalsidase in participants with Fabry disease. Agalsidase beta and agalsidase alfa were studied alongside migalastat doses of 150 mg and 450 mg. The arm descriptions include agalsidase beta doses of 0.5 mg/kg and 1.0 mg/kg and an agalsidase alfa dose of 0.2 mg/kg.
The registry describes Period 1 and Period 2 in stages. Blood collection for the primary pharmacokinetic endpoint included samples before agalsidase infusion, samples over a 24-hr period after infusion, and follow-up samples on Days 2, 7, and 14. In Period 2, the sampling schedule also included times before and after migalastat dosing and around agalsidase infusion. This design supports measuring enzyme concentration over time under the listed treatment conditions.
Because allocation was non-randomized and treatment was unmasked, this is not a randomized comparison with a like-for-like control group. The treatments were given sequentially, so interpretation must account for the order and period structure rather than treating each group as an independent randomized arm. The registry record does not report a protocol-level explanation of how treatment order was selected, whether order effects were formally assessed, or how period effects were handled in the analysis.
The study record identifies 11 outcome measures and 13 analyses. It gives a primary pharmacokinetic endpoint and a secondary outcome concerning change from baseline to Day 7 in active α-Gal A in skin following agalsidase alone and co-administration with migalastat. Detailed numerical results for the primary outcome are not reported in the registry record. A sample-size justification and a full statistical analysis plan are also not reported in the registry record, so the rationale for enrollment and the prespecified analysis choices cannot be established from the 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: The total number of unique participants in this study was 20: 3 from Stage 1 were re-enrolled and newly identified in Stage 2. Of those, 1 initially received 0.5 milligrams (mg)/kilogram (kg) agalsidase beta; after resolution of an agalsidase beta shortage, their dose was increased to 1.0 mg/kg; all remaining visits were completed at this dose.
Stage 1: Period 1
| Stage | Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) | Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) |
|---|---|---|---|---|---|---|
| STARTED | 5 | 3 | 4 | 0 | 0 | 0 |
| PK Population | 5 | 3 | 4 | 0 | 0 | 0 |
| Received at Least 1 Dose of Study Drug | 5 | 3 | 4 | 0 | 0 | 0 |
| COMPLETED | 5 | 3 | 4 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Stage 1: Period 2
| Stage | Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) | Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) |
|---|---|---|---|---|---|---|
| STARTED | 5 | 3 | 4 | 0 | 0 | 0 |
| PK Population | 5 | 3 | 4 | 0 | 0 | 0 |
| COMPLETED | 5 | 3 | 4 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Stage 1: Period 3
| Stage | Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) | Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) |
|---|---|---|---|---|---|---|
| STARTED | 5 | 3 | 4 | 0 | 0 | 0 |
| COMPLETED | 5 | 3 | 4 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Stage 2: Period 1
| Stage | Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) | Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 2 | 5 | 4 |
| Received at Least 1 Dose of Study Drug | 0 | 0 | 0 | 2 | 5 | 4 |
| PK Population | 0 | 0 | 0 | 1 | 5 | 4 |
| COMPLETED | 0 | 0 | 0 | 2 | 5 | 4 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population.
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 agalsidase or migalastat. All safety analyses were performed using this set. Participants were analyzed according to treatment received. Three participants from Stage 1 were re-enrolled and newly identified in Stage 2, with 1 receiving both 0.5 and 1.0 mg/kg agalsidase beta.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) | Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 5 | 3 | 4 | 2 | 6 | 4 | |
| Age, Continuous: Stage 1 | years | 50.6 (SD 6.88) | 45.7 (SD 8.02) | 43.5 (SD 5.07) | — | — | — |
| Age, Continuous: Stage 2 | years | — | — | — | 53.5 (SD 2.12) | 38.7 (SD 12.16) | 38.5 (SD 9.15) |
| Sex: Female, Male: Stage 1 – Female | Participants | 0 | 0 | 0 | — | — | — |
| Sex: Female, Male: Stage 1 – Male | Participants | 5 | 3 | 4 | — | — | — |
| Sex: Female, Male: Stage 2 – Female | Participants | — | — | — | 0 | 0 | 0 |
| Sex: Female, Male: Stage 2 – Male | Participants | — | — | — | 2 | 6 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Change In Area Under The Plasma Concentration Versus Time Curve (AUC) For Active α-Galactosidase A (α-Gal A) Levels After Administration Of Migalastat, measured over 0 hr, 2 hr, 2 days, 7 days, 14 days post dose.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | hr*[nmol/hr/mL] |
| Endpoint classification | Continuous Endpoint |
The primary endpoint concerns change in the area under the plasma concentration-versus-time curve for active α-Gal A after administration of migalastat. The assay measured the rate of enzyme activity using an artificial, fluorescent substrate. The record describes AUC extrapolated from time 0 to infinity and AUC through the last time point with a quantified concentration. Its stated unit is hr*[nmol/hr/mL].
In general, an area under a concentration-time curve combines measurements across the sampling period into a summary of exposure over time. It can describe pharmacokinetic behavior more comprehensively than a measurement at a single time point. Here, the measured plasma enzyme activity is used as an indicator of agalsidase pharmacokinetics, and the study question is whether that measure changes with migalastat co-administration.
Sampling was planned around the agalsidase infusion and included later measurements on Days 2, 7, and 14. Period 2 sampling also captured time points around migalastat dosing. The registry identifies the endpoint summary as a mean with standard deviation, but numerical endpoint estimates and variability are not reported in the registry record. Without those results, the size, direction, and precision of any difference in AUC cannot be characterized.
The endpoint is a pharmacokinetic measure, not a direct measure of symptoms or clinical benefit. A change in the enzyme activity curve would describe the measured plasma response under the studied conditions; it would not, by itself, establish what that response means for health outcomes.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the scientific question and the planned pharmacokinetic measure, but it does not report numerical results for the primary endpoint. There is therefore no reported mean change, standard deviation, confidence interval, or p-value with which to describe the size, direction, or precision of the primary finding. The record’s description of a mean and standard deviation identifies the intended summary format, not the observed result.
This gap matters because the study’s central question is comparative: whether agalsidase exposure, as reflected by active α-Gal A activity over time, differs when migalastat is given. A description of the sampling schedule and assay explains how the measure was obtained, but does not establish whether the curve changed. The same caution applies to the reciprocal question about agalsidase’s effect on migalastat pharmacokinetics: numerical results for that question are not reported in the registry record.
The design also limits what can be inferred from any apparent contrast among the listed treatment conditions. The study was non-randomized, open-label, and sequential. Treatment conditions were not allocated as a randomized, like-for-like control comparison. Period, order, or other time-related differences could therefore complicate interpretation; whether these factors were assessed or adjusted is not reported in the registry record. The study’s enrollment of 20 also means the record describes a small study, but it does not provide enough outcome information to quantify uncertainty around the primary result.
The posted safety figures are descriptive and vary across the listed stage and period groups. One group reports a serious adverse event for 1 of 2 participants at risk; the other listed groups report no serious adverse events. These group counts should not be collapsed into a comparative treatment effect: the group sizes differ, the periods and regimens differ, and the design was not randomized. The registry lists Acroparaesthesia as a top serious term at 50.0%, but does not report its group allocation alongside that term.
In general, a confidence interval communicates a range of values compatible with the data under the analysis assumptions, while a p-value summarizes how unusual data would be under a specified null hypothesis. Neither can substitute for the estimated effect or resolve biases arising from design. No primary endpoint interval or test result is reported in the registry record. Accordingly, the posted record supports describing the research question, methods, and listed safety counts, but not concluding whether the measured pharmacokinetic interaction was large, small, or absent.
The study should not be read as a definitive comparison of treatment strategies or clinical outcomes. Its stated focus is pharmacokinetics and safety under sequential dosing conditions. The registry record does not report clinical outcome estimates or a numerical primary pharmacokinetic result that would support a broader conclusion.
9. Statistical Methods Explained
The registry identifies a continuous primary measure summarized as a mean with standard deviation. The measure is the change in AUC for active α-Gal A levels after migalastat administration. The study was open-label, non-randomized, and sequential, and its pharmacokinetic population was defined by evaluable parameter data and completion of at least Period 1 and Period 2 in any stage.
What does an AUC measure?
In general, an area under the curve summarizes measurements collected over time. For a concentration-time curve, the AUC reflects the overall exposure represented by the measured concentrations during the sampling interval. It combines information from multiple time points, so it can capture a pattern that a single measurement might miss. The registry describes AUC extrapolated from time 0 to infinity and AUC through the last time point at which concentration was quantified. The record does not include the numerical AUC estimates.
For this endpoint, the assay measured active α-Gal A enzyme activity in plasma using an artificial, fluorescent substrate. The result is therefore an assay-based measure of enzyme activity over time. The endpoint is intended to characterize agalsidase plasma pharmacokinetics and the effect of migalastat on that measure. It does not directly measure a patient-centered clinical outcome.
Why report a mean and standard deviation?
In general, the mean describes the center of a set of continuous observations, while the standard deviation describes how spread out individual observations are around that center. Reporting both can help readers distinguish an estimated average response from the variability among participants. A standard deviation is not the same as a confidence interval: the former describes dispersion in the observations, while the latter expresses uncertainty around an estimate under an analysis model. The registry specifies mean and standard deviation as the summary approach, but does not report the actual values for the primary measure.
Means can be useful for continuous pharmacokinetic outcomes, but their interpretation depends on the data and analysis. AUC values may vary across individuals, and the registry record does not report distributional diagnostics, transformations, or model details. Those decisions and checks are not reported in the registry record, so it is not possible to judge whether the analysis addressed skew or other features of the observed data.
What does sequential, non-randomized allocation imply?
In general, randomization helps balance measured and unmeasured participant characteristics across treatment groups. This study was non-randomized, so that protection cannot be assumed. The sequential design means treatment conditions occurred in periods rather than being described as randomized parallel groups. When measurements are made under different periods, changes may reflect treatment, period, order, or other time-related influences. Whether the analysis modeled within-participant correlation, period effects, or order effects is not reported in the registry record.
Open-label means the study was not masked. In general, knowledge of treatment assignment can affect behavior, reporting, or assessment, although an enzyme assay is an objective laboratory measure. The record does not report procedures intended to reduce or assess possible effects of unmasked treatment assignment.
How should the sample-size illustration be understood?
The stated sample-size illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes planning for a stated fraction of an observed effect. In general, such an illustration asks how many participants per arm might be needed under those assumptions to detect a specified effect. It is not the trial’s own sample-size justification, and the registry record does not report the protocol’s sample-size rationale.
These planning values are illustrations rather than observed power. They do not show the probability that this completed study detected an effect, and they do not establish that an effect exists. The record’s sample-size assumptions state that the target effect is a fraction of the observed effect, but the numerical primary outcome estimate needed to interpret that basis is not reported in the registry record. The actual enrollment was 20.
What can be inferred from the available analysis information?
The registry reports 11 outcome measures and 13 analyses. It names the primary endpoint and one secondary outcome concerning skin active α-Gal A change from baseline to Day 7. The description is not a substitute for a complete statistical analysis plan. The record does not report the hypothesis-testing procedure for the primary endpoint, model covariates, treatment of repeated measures, handling of outliers, or confidence-interval method. These details are not reported in the registry record.
In general, analysis methods should match the study design and the structure of the observations. Sequential pharmacokinetic measurements may be related within a participant, and a valid analysis needs to account for the relevant dependence if the model requires it. The posted registry information does not specify how that dependence was handled. Without the numerical endpoint results and model details, interpretation should remain descriptive rather than implying an adjusted or causal treatment effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies 11 outcome measures and 13 analyses. It reports a primary pharmacokinetic endpoint and a secondary outcome for change from baseline to Day 7 in active α-Gal A in skin following agalsidase alone and co-administration with migalastat. The record does not report whether statistical testing was adjusted for multiple outcomes or analyses, whether any outcomes were designated exploratory, or how the primary and secondary analyses were prioritized beyond their labels. These multiplicity procedures are not reported in the registry record.
In general, examining multiple outcomes or analyses can increase the chance of a nominally unusual result arising by chance. Adjustment methods or a clearly prespecified hierarchy can help control interpretation, but the registry does not document such a procedure. Because numerical primary results and inferential statistics are also not reported, multiplicity cannot be evaluated against the actual outcome findings.
The pharmacokinetic population included participants with evaluable pharmacokinetic parameter data who successfully completed at least Period 1 and Period 2 in any stage. This definition indicates that not every enrolled participant necessarily qualified for that analysis population. The number included in each pharmacokinetic analysis, reasons for missing or unevaluable data, and methods for handling missing measurements are not reported in the registry record.
In general, missing data can affect both precision and the representativeness of an analysis, especially when missingness is related to treatment, participant characteristics, or observed outcomes. The registry record does not describe imputation, sensitivity analyses, or assumptions about missingness. It also does not report whether analyses other than the pharmacokinetic analyses used different populations. These omissions limit assessment of how the analyzed participants may differ from the enrollment group and how robust the reported results would be to missing data.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Stage 1 Pd 1: 0.5 mg/kg Agal-B (Arm 1) | 0 | 5 | 0.0% |
| Stage 1 Pd 2: 150 mg Mig Before 0.5 mg/kg Agal-B (Arm 1) | 0 | 5 | 0.0% |
| Stage 1 Pd 3: 150 mg Mig (Arm 1) | 0 | 5 | 0.0% |
| Stage 1 Pd 1: 1.0 mg/kg Agal-B (Arm 2) | 0 | 3 | 0.0% |
| Stage 1 Pd 2: 150 mg Mig Before 1.0 mg/kg Agal-B (Arm 2) | 0 | 3 | 0.0% |
| Stage 1 Pd 3: 150 mg Mig (Arm 2) | 0 | 3 | 0.0% |
| Stage 1 Pd 1: 0.2 mg/kg Agal-A (Arm 3) | 0 | 4 | 0.0% |
| Stage 1 Pd 2: 150 mg Mig Before 0.2 mg/kg Agal-A (Arm 3) | 0 | 4 | 0.0% |
| Stage 1 Pd 3: 150 mg Mig (Arm 3) | 0 | 4 | 0.0% |
| Stage 2 Pd 1: 0.5 mg/kg Agal-B (Arm 4) | 1 | 2 | 50.0% |
| Stage 2 Pd 2: 450 mg Mig Before 0.5 mg/kg Agal-B (Arm 4) | 0 | 1 | 0.0% |
| Stage 2 Pd 1: 1.0 mg/kg Agal-B (Arm 5) | 0 | 6 | 0.0% |
| Stage 2 Pd 2: 450 Mig Before 1.0 mg/kg Agal-B (Arm 5) | 0 | 6 | 0.0% |
| Stage 2 Pd 1: 0.2 mg/kg Agal-A (Arm 6) | 0 | 4 | 0.0% |
| Stage 2 Pd 2: 450 Mig Before 0.2 mg/kg Agal-A (Arm 6) | 0 | 4 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Stage 1 Pd 1: 0.5 mg/kg Agal-B (Arm 1) | 4 of 5 |
| Stage 1 Pd 2: 150 mg Mig Before 0.5 mg/kg Agal-B (Arm 1) | 0 of 5 |
| Stage 1 Pd 3: 150 mg Mig (Arm 1) | 3 of 5 |
| Stage 1 Pd 1: 1.0 mg/kg Agal-B (Arm 2) | 3 of 3 |
| Stage 1 Pd 2: 150 mg Mig Before 1.0 mg/kg Agal-B (Arm 2) | 2 of 3 |
| Stage 1 Pd 3: 150 mg Mig (Arm 2) | 0 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Stage 1 Pd 1: 0.5 mg/kg Agal-B (Arm 1) | Stage 1 Pd 2: 150 mg Mig Before 0.5 mg/kg Agal-B (Arm 1) | Stage 1 Pd 3: 150 mg Mig (Arm 1) | Stage 1 Pd 1: 1.0 mg/kg Agal-B (Arm 2) | Stage 1 Pd 2: 150 mg Mig Before 1.0 mg/kg Agal-B (Arm 2) | Stage 1 Pd 3: 150 mg Mig (Arm 2) |
|---|---|---|---|---|---|---|---|
| Acroparaesthesia | Nervous system disorders | 0 of 5 | 0 of 5 | 0 of 5 | 0 of 3 | 0 of 3 | 0 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Stage 1 Pd 1: 0.5 mg/kg Agal-B (Arm 1) | Stage 1 Pd 2: 150 mg Mig Before 0.5 mg/kg Agal-B (Arm 1) | Stage 1 Pd 3: 150 mg Mig (Arm 1) | Stage 1 Pd 1: 1.0 mg/kg Agal-B (Arm 2) | Stage 1 Pd 2: 150 mg Mig Before 1.0 mg/kg Agal-B (Arm 2) | Stage 1 Pd 3: 150 mg Mig (Arm 2) |
|---|---|---|---|---|---|---|---|
| Cardiac murmur | Investigations | 2 of 5 | 0 of 5 | 0 of 5 | 0 of 3 | 0 of 3 | 0 of 3 |
| Atrial flutter | Cardiac disorders | 1 of 5 | 0 of 5 | 0 of 5 | 0 of 3 | 0 of 3 | 0 of 3 |
| Angina pectoris | Cardiac disorders | 0 of 5 | 0 of 5 | 0 of 5 | 0 of 3 | 1 of 3 | 0 of 3 |
| Supraventricular extrasystoles | Cardiac disorders | 0 of 5 | 0 of 5 | 0 of 5 | 1 of 3 | 0 of 3 | 0 of 3 |
| Ear canal erythema | Ear and labyrinth disorders | 0 of 5 | 0 of 5 | 1 of 5 | 0 of 3 | 0 of 3 | 0 of 3 |
| Tympanic membrane disorder | Ear and labyrinth disorders | 0 of 5 | 0 of 5 | 1 of 5 | 0 of 3 | 0 of 3 | 0 of 3 |
| Dental caries | Gastrointestinal disorders | 0 of 5 | 0 of 5 | 1 of 5 | 0 of 3 | 0 of 3 | 0 of 3 |
| Diarrhoea | Gastrointestinal disorders | 0 of 5 | 0 of 5 | 0 of 5 | 0 of 3 | 1 of 3 | 0 of 3 |
| Faeces pale | Gastrointestinal disorders | 0 of 5 | 0 of 5 | 0 of 5 | 0 of 3 | 1 of 3 | 0 of 3 |
| Oedema peripheral | General disorders | 1 of 5 | 0 of 5 | 0 of 5 | 0 of 3 | 0 of 3 | 0 of 3 |
Serious events with the highest arm-level rate: acroparaesthesia (50.0%).
The safety record lists serious adverse events by stage, period, and treatment group. Most listed groups report 0 serious adverse events among the participants at risk. The exception is Stage 2 Period 1, 0.5 mg/kg agalsidase beta, Arm 4, which reports 1 serious adverse event among 2 participants at risk. These are small, group-specific counts and should be read descriptively.
The groups differ in regimen and number at risk, and the study was non-randomized and sequential. The figures therefore do not establish a comparative safety effect between treatments. No deaths are reported as numerical counts; death counts are not reported in the registry record. The registry lists Acroparaesthesia as a top serious adverse event term at 50.0%, but does not report which group the term belongs to or a matching participant count alongside it.
In general, a count among participants at risk describes the number of participants with an event in that listed group; it does not by itself show whether treatment caused the event. Small group counts are particularly limited for estimating uncommon events or comparing risk. The registry’s serious-event figures should not be interpreted as a complete assessment of safety beyond the listed groups and reported information.
12. What the Result Does, and Does Not, Mean
The study is designed to characterize a pharmacokinetic interaction: whether migalastat changes agalsidase-related active α-Gal A activity in plasma over time, and whether agalsidase changes migalastat safety and pharmacokinetics. The registry specifies the assay, sampling periods, intervention doses, and pharmacokinetic analysis population. These details explain the question and the intended measurement.
The record does not report numerical primary endpoint results. It therefore does not establish the direction or magnitude of a change in AUC, the precision of an estimate, or whether an analysis found evidence against a null hypothesis. The same limitation applies to numerical results for the reciprocal pharmacokinetic question. The stated endpoint and study objective should not be mistaken for evidence that an interaction was or was not observed.
The posted safety figures report serious adverse event counts for individual stage and period groups. Those counts vary by group and are not a randomized comparison. The record lists Acroparaesthesia among top serious terms, but does not connect that term to a specific group in the reported information. Such descriptive reporting does not establish causality or permit a reliable comparison of safety between regimens.
In general, a pharmacokinetic result can describe exposure or measured concentration patterns, but it does not alone establish a clinical benefit or harm. This study’s primary measure concerns plasma enzyme activity, not a clinical outcome. Its secondary outcome concerns active α-Gal A in skin, but numerical results for that outcome are not reported in the registry record.
The study is completed and reports an enrollment of 20, but the registry record does not provide enough numerical outcome information to determine how precisely the primary question was answered. The design and reporting do not support broad conclusions about treatment effectiveness or a definitive comparison of regimens. Interpretation should remain limited to the methods and outcome information actually reported.
13. Why This Trial Matters Statistically
This study is statistically informative because it illustrates the difference between a clearly described pharmacokinetic question and a result that can be quantitatively interpreted. The registry specifies active α-Gal A AUC as the primary measure, gives the assay and sampling schedule, and identifies the pharmacokinetic population. Yet without numerical endpoint estimates or their variability, the magnitude and precision of the primary result cannot be assessed.
The sequential, non-randomized design also makes the comparison structure important. Treatment conditions were not assigned as a randomized, like-for-like control comparison. Readers must therefore distinguish a within-study pharmacokinetic question from a randomized treatment effect, and consider that period or order influences may matter. Whether the analysis addressed those influences is not reported in the registry record.
The registry’s 11 outcome measures and 13 analyses raise a general issue of multiplicity: when multiple outcomes or analyses are considered, the approach to interpretation should be clear. The record does not report a multiplicity procedure or a complete analysis plan. This absence, combined with unreported primary estimates, limits statistical appraisal.
The safety information is another reminder that raw event counts are not automatically comparative evidence. Group sizes differ, and the listed groups correspond to different stages, periods, and regimens. The serious adverse event counts can be described, but they do not establish differences in risk.
Finally, the sample-size assumptions are explicitly planning illustrations rather than observed power. In general, a planning calculation depends on assumptions about the effect and analysis; it cannot retroactively prove that a completed study was adequately powered. The stated illustration should be separated from the actual enrollment and from any inference about the primary outcome. Together, these features make transparent reporting of estimates, uncertainty, analysis populations, and design assumptions essential to judging what the evidence supports.
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 the primary question is that numerical pharmacokinetic results are not reported in the registry record. No mean AUC change, standard deviation, confidence interval, or p-value is available to characterize the result. The registry describes the endpoint and assay, but the measurement method alone does not reveal the observed effect.
The study was non-randomized, open-label, and sequential. It was not a randomized, like-for-like control comparison, and the record does not report whether period or order effects were modeled or otherwise evaluated. The number enrolled was 20, while the pharmacokinetic population required evaluable data and successful completion of at least Period 1 and Period 2 in any stage. Analysis-specific participant counts and reasons for missing or unevaluable data are not reported in the registry record.
The registry identifies 11 outcome measures and 13 analyses, but does not report a complete analysis plan or a multiplicity approach. Details about the statistical model, treatment of repeated observations, handling of missing data, and sensitivity analyses are not reported in the registry record. This prevents assessment of whether the analysis choices adequately reflected the sequential design and data structure.
Safety counts are listed by stage, period, and regimen, with different numbers at risk. They are descriptive and do not support randomized comparisons. Death counts are not reported in the registry record, and the listed top serious adverse event term is not linked to a specific group in the reported information. These limitations constrain both comparative safety interpretation and the overall assessment of the interaction question.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Drug-Drug Interaction Study Between AT1001 (Migalastat Hydrochloride) and Agalsidase in Participants With Fabry Disease — NCT01196871.
- Registry record last updated 2018-12-19; status last verified 2018-11.
- Results first posted 2018-11-01.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01196871 is a completed, open-label, non-randomized Phase 2A sequential study of migalastat and agalsidase in participants with Fabry disease. The registry reports an enrollment of 20. The interventions include migalastat at 150 mg or 450 mg, agalsidase beta at 0.5 mg/kg or 1.0 mg/kg, and agalsidase alfa at 0.2 mg/kg.
The primary endpoint is change in AUC for active α-Gal A levels in plasma after migalastat administration. The record describes the assay, sampling schedule, and pharmacokinetic population, but numerical primary endpoint results are not reported in the registry record. It also identifies 11 outcome measures and 13 analyses without reporting a complete statistical analysis plan or multiplicity procedure.
Serious adverse event counts are reported for stage and period groups; most list no serious events, while one lists 1 among 2 participants at risk. These descriptive data do not establish comparative effects. Overall, the registry describes the study question and methods but does not report enough numerical outcome information to quantify the primary pharmacokinetic finding.