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 Study to Evaluate the Safety of AT2220 (Duvoglustat) in Pompe Disease (NCT00688597), a non-randomized phase 2 study. The primary outcome is Proportion Of Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00688597 |
| Phase | Phase 2 |
| Condition | Pompe Disease |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amicus Therapeutics |
| Results posted | Yes |
2. Clinical Question
Population
Participants with Pompe disease who received at least one dose of duvoglustat formed the safety population. The registry reports enrollment of 3.
Intervention
Oral duvoglustat (AT2220) was given in three regimens: low-dose 2.5 grams on scheduled dosing days, or high-dose 5.0 g on either of two schedules.
Comparator
The cohorts received different regimens, but the study was nonrandomized and had no masking. The registry does not describe a like-for-like control comparison.
Primary question
The primary endpoint was the proportion of participants experiencing severe treatment-emergent adverse events during the study timeframe. The endpoint result is not reported in the registry record.
The study also evaluated duvoglustat’s effects on functional parameters. The listed secondary outcome was change in the 6-minute Walk Test (6MWT) from baseline to end of study; a result for that outcome is not reported in the registry record. The central interpretive question is therefore what can be learned from the safety information that is actually reported, and how far it can address the stated primary question.
The registry gives separate dosing schedules for three cohorts, but this was not a randomized comparison. Differences between cohorts cannot be attributed to dose or schedule alone from the reported information. The primary endpoint concerns severity, whereas the adverse-event summary separately reports serious and other non-serious events. Those categories should not be treated as interchangeable. The available safety counts provide context about reported events, but do not substitute for the missing result for severe treatment-emergent adverse events.
3. Trial Design
This was a phase 2, open-label, multicenter study of oral AT2220 (duvoglustat) in participants with Pompe disease. It used a nonrandomized parallel-cohort design with no masking. The registry records enrollment of 3 and lists the study status as terminated. The start date was 2008-12-08, and the primary completion date was 2009-12-14. The reason for termination is not reported in the registry record.
The three cohorts were assigned different regimens. Cohort 1 received 2.5 grams once a day for 3 days, followed by no drug for 4 days, for 11 weeks. Cohort 2 received 5.0 g once a day for 3 days, followed by no drug for 4 days, for 11 weeks. Cohort 3 received 5.0 g once a day for 7 days, followed by no drug for 7 days, for 11 weeks. The registry identifies duvoglustat as the drug intervention.
Because allocation was nonrandomized, cohort membership should not be interpreted as if it arose from random assignment. The registry does not report a concurrent placebo or untreated control cohort. Open-label status means the study was not masked; the registry does not describe additional procedures to reduce awareness of treatment assignment.
The main stated purpose was to evaluate safety and tolerability across the dosing regimens. The registry also describes evaluation of functional parameters, and lists change in 6MWT from baseline to end of study as a secondary outcome. It does not report cohort-specific recruitment details, the reason for selecting the regimens, or a statistical analysis plan. These omissions limit how fully the study’s design choices and intended comparisons can be assessed.
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
| Stage | Cohort 1 | Cohort 2 | Cohort 3 |
|---|---|---|---|
| STARTED | 3 | 0 | 0 |
| Received at Least 1 Dose of Study Drug | 3 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 0 | 0 |
Reasons for not completing this period:
| Reason | Cohort 1 | Cohort 2 | Cohort 3 |
|---|---|---|---|
| Adverse Event | 2 | 0 | 0 |
| Physician Decision | 1 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Population: All participants who received at least 1 dose of duvoglustat.
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 duvoglustat.
| Characteristic | Unit | Cohort 1 | Cohort 2 | Cohort 3 | Total |
|---|---|---|---|---|---|
| Participants analysed | 3 | 0 | 0 | 3 | |
| Age, Continuous | years | 49.07 (SD 11.02) | — | — | 49.07 (SD 11.02) |
| Sex: Female, Male: Female | Participants | 2 | — | — | 2 |
| Sex: Female, Male: Male | Participants | 1 | — | — | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Proportion Of Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs), measured over Baseline, Week 11.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled the proportion of participants experiencing severe treatment-emergent adverse events (TEAEs). It concerns participants who received duvoglustat, with the stated timeframe of baseline to Week 11. The registry defines an adverse event as an unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during observation. It describes severe intensity as incapacitating and requiring medical intervention.
A participant-based endpoint counts whether each participant experienced an event meeting the endpoint definition. It is different from counting every event episode: a participant may experience more than one event, while the endpoint’s unit is participants. In general, this kind of summary is useful for describing how often a specified safety outcome occurred in the population evaluated. It does not, by itself, establish that an event was caused by the study drug.
The primary endpoint’s result is not reported in the registry record. The adverse-event summary separately reports participants with serious events and with other non-serious events. Seriousness and severity are distinct concepts, so those figures cannot be used as the severe-TEAE result. The record’s definition of severe intensity is not a replacement for an endpoint count. The registry also points to a separate adverse-events module for summaries of serious and other non-serious events regardless of causality.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies severe treatment-emergent adverse events as the primary endpoint, but does not report a result for that endpoint. Accordingly, the posted safety counts should not be presented as the primary endpoint finding. The record’s adverse-event summary lists 2 participants affected by serious events among 3 at risk in Cohort 1, and 3 participants affected by other non-serious events among 3 at risk in Cohort 1. Cohorts 2 and 3 have 0 participants listed at risk in those summaries. The registry does not provide the severe-TEAE count by cohort in the registry record described for this study.
These are descriptive counts, not evidence of a comparative treatment effect. The design was nonrandomized, and the registry describes no like-for-like control comparison. The groups received different dosing schedules, and the adverse-event summary lists no participants at risk in Cohorts 2 and 3. Thus the reported information does not support a reliable comparison of safety across the three regimens. The registry does not explain why those cohorts have zero participants at risk in the adverse-event summary.
The serious-event summary names muscular weakness as a top serious-event term and gives 66.7%. The denominator or calculation basis for that percentage is not reported in the registry record. It should therefore be read as a registry-listed descriptive percentage, not as a risk estimate that can be independently reconstructed from the information. The record does not establish whether any reported event was caused by duvoglustat; the adverse-event summaries are described as regardless of causality.
Precision is also a central concern. With only a small reported enrollment and no reported primary endpoint estimate or confidence interval, the amount of uncertainty around the severe-TEAE frequency cannot be assessed from the registry record. A count alone does not show how stable the estimated frequency would be in a larger group. No inferential analysis result is listed in the registry record.
The listed secondary outcome is change in 6MWT from baseline to end of study, but its result is not reported in the registry record. No conclusion about functional change can be drawn from the outcome title alone. Overall, the registry documents the intended safety question, regimen descriptions, and limited adverse-event counts; it does not provide enough reported endpoint information to quantify the primary outcome or compare regimens.
9. Statistical Methods Explained
What does a participant-count endpoint represent?
For a binary safety endpoint, each participant is classified according to whether the defined event occurred during the specified observation period. A proportion uses the number of participants meeting the definition relative to the participants evaluated for that endpoint. This is a participant-level summary, not a count of event episodes. If an individual experiences multiple qualifying events, the participant-level endpoint still concerns whether that participant experienced the outcome.
Here, the primary endpoint is the proportion experiencing severe TEAEs, but its result is not reported in the registry record. The serious and other non-serious event counts are distinct summaries. They do not supply the missing numerator or denominator for the severe-TEAE endpoint. The registry reports a safety population defined as participants who received at least one dose of duvoglustat, but does not give the primary endpoint’s cohort-level result.
Why distinguish severity from seriousness?
In general, severity describes the intensity of an event, while seriousness is a separate classification used in safety reporting. A severe event is not necessarily classified as serious, and a serious event is not necessarily severe under the study’s intensity grading. The registry describes severe intensity as incapacitating and requiring medical intervention. It separately presents serious and other non-serious adverse events. Treating the serious-event count as the severe-TEAE count would therefore conflate different classifications.
What can counts and percentages tell a reader?
Counts show how many participants were recorded as affected in the stated group. A percentage can communicate a proportion, but it depends on its denominator and on how the event category was defined. The top serious-event term is listed as muscular weakness at 66.7%; the calculation basis is not reported in the registry record. Without a stated denominator, that percentage cannot be independently checked using the reported information. Counts and percentages are descriptive: they do not by themselves establish causation or show that one regimen differs from another.
In general, a confidence interval expresses uncertainty around an estimate. It can help readers distinguish a precise estimate from one that is compatible with a wide range of underlying event frequencies. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated from such an interval. A small observed count does not automatically mean that the underlying frequency is low; the amount of information depends on the number evaluated and the completeness of outcome reporting.
Why does the design affect interpretation?
Random allocation is one way to make treatment groups comparable in expectation. This study was nonrandomized, and the cohorts received different regimens. In general, differences between nonrandomized groups may reflect differences in who entered each cohort, as well as differences in regimen. The registry does not report enough information to assess those possible differences. It also lists no participants at risk for the adverse-event summaries in Cohorts 2 and 3, so the reported summaries cannot support a comparison across all regimens.
Open-label status means masking was absent. In general, awareness of treatment assignment can influence event recognition, reporting, or assessment, depending on the outcome and study procedures. The registry does not describe procedures to assess or mitigate such influences. This does not show that reporting was biased; it identifies a potential interpretive limitation that cannot be evaluated with the information recorded.
How should statistical testing and planning be read?
The registry lists 0 analyses. It does not report a statistical test, a model for the primary endpoint, an adjusted estimate, or a confidence interval. Thus, there is no reported inferential result to interpret. General statistical practice may use confidence intervals and prespecified analyses to express uncertainty and define how outcomes are evaluated, but the analysis plan for this study is not reported in the registry record.
The registry describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. These assumptions describe a planning exercise, not the trial’s own design or an observed-power result. The study’s enrollment was not a randomized two-arm comparison, so such illustrations should not be read as evidence that this study had adequate power for its primary endpoint. A sample-size illustration is a planning aid and does not recover a missing endpoint result.
Why can over-dispersion matter in general?
For outcomes that count events, a simple model may assume that variability follows a particular relationship to the mean. Over-dispersion means the observed variability is greater than that model expects; ignoring it can make uncertainty appear smaller than it is. This study’s primary endpoint is defined in terms of participants experiencing an event, and the registry does not report an event-count model or an analysis addressing over-dispersion. This general concept should not be mistaken for a method documented for this trial.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Cohort 1 | 3 | 1 | 33.3% | 0.8% to 90.6% | 6.1% to 79.2% | 6.8% to 80.6% |
R code and output
arm <- c("Cohort 1")
n <- c(3)
events <- c(1)
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 Cohort 1 3 1 33.3 0.8 90.6 6.1 79.2 6.8 80.611. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures, identifies severe TEAEs as the primary endpoint, and lists change in 6MWT from baseline to end of study as a secondary outcome. It does not report a multiplicity plan describing how interpretation would account for assessing more than one outcome. The statistical analysis plan is not reported in the registry record, so it is not possible to determine whether outcomes were prioritized beyond the primary and secondary labels or whether any adjustment was planned.
The registry defines the safety population as participants who received at least one dose of duvoglustat. The adverse-event summaries list 3 at risk in Cohort 1 and 0 at risk in Cohorts 2 and 3. The record does not explain the zero at-risk entries for the latter cohorts. It also does not report the number evaluated for the primary endpoint by cohort or explain how participants with incomplete outcome information were handled.
Missing-data methods, reasons for missing observations, and any sensitivity analyses are not reported in the registry record. The record does not describe an analysis population for the 6MWT outcome or give its result. These gaps matter because the number and characteristics of participants with observed outcomes can affect how descriptive estimates are interpreted. No inference about the reason for absent cohort entries or missing outcome information is justified by the registry entries alone.
The registry lists 0 analyses. It therefore does not provide a reported analysis set, outcome-specific handling rules, or inferential procedures for evaluating multiplicity and missing data. Those details should not be inferred from the outcome labels or from the adverse-event summaries.
12. 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 |
|---|---|---|---|
| Cohort 1 | 2 | 3 | 66.7% |
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 |
|---|---|
| Cohort 1 | 3 of 3 |
| Cohort 2 | 0 of 0 |
| Cohort 3 | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1 | Cohort 2 | Cohort 3 |
|---|---|---|---|---|
| Muscular weakness | General disorders | 2 of 3 | 0 of 0 | 0 of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 | Cohort 2 | Cohort 3 |
|---|---|---|---|---|
| Alanine aminotransferase increased | General disorders | 3 of 3 | 0 of 0 | 0 of 0 |
| Aspartate aminotransferase increased | General disorders | 3 of 3 | 0 of 0 | 0 of 0 |
| Blood creatine phosphokinase increased | General disorders | 3 of 3 | 0 of 0 | 0 of 0 |
| Muscular weakness | General disorders | 2 of 3 | 0 of 0 | 0 of 0 |
| Fall | General disorders | 2 of 3 | 0 of 0 | 0 of 0 |
| Flatulence | General disorders | 1 of 3 | 0 of 0 | 0 of 0 |
| Abdominal pain upper | General disorders | 1 of 3 | 0 of 0 | 0 of 0 |
| Dysphagia | General disorders | 1 of 3 | 0 of 0 | 0 of 0 |
| Joint injury | General disorders | 1 of 3 | 0 of 0 | 0 of 0 |
Serious events with the highest arm-level rate: muscular weakness (66.7%).
The adverse-event summary distinguishes serious events from other non-serious events. In Cohort 1, it lists 2 participants affected by serious events among 3 at risk, and 3 participants affected by other non-serious events among 3 at risk. Cohorts 2 and 3 are listed with 0 participants at risk and 0 affected in these summaries. The registry does not explain the zero at-risk entries for those cohorts.
The serious-event term listed at the top is muscular weakness, with 66.7%. The basis for that percentage is not reported in the registry record. The event summary is described as covering events regardless of causality, so these figures do not establish that duvoglustat caused the events. A participant may also appear in more than one event category; the record does not state whether the serious and other-event groups overlap. Their counts should not be added together.
These figures are not the primary endpoint result. The primary endpoint concerns severe TEAEs, while the adverse-event summary classifies serious and other non-serious events. The concepts are not interchangeable. Deaths are not reported in the registry record. The counts are descriptive and, given the nonrandomized design and the reported at-risk entries, do not provide a sound basis for comparing regimen safety.
13. What the Result Does, and Does Not, Mean
The registry record documents a phase 2 study intended to evaluate the safety and tolerability of three oral duvoglustat regimens in Pompe disease. It gives the dosing schedules and identifies severe treatment-emergent adverse events as the primary endpoint. It also provides a limited adverse-event summary for Cohort 1 and names muscular weakness as a top serious-event term. These registry entries describe what the record reports; they do not constitute a complete estimate of the primary endpoint.
The primary endpoint result is not reported in the registry record. The serious-event and other non-serious-event counts cannot fill that gap because seriousness and severity are distinct classifications. Nor can the available counts establish whether an event was caused by duvoglustat: the summaries are described as regardless of causality. The record does not report the result for the secondary 6MWT outcome, so no conclusion about functional change is supported by the listed outcome title.
The record also does not establish a comparative safety effect among the regimens. Allocation was nonrandomized, and the adverse-event summaries list no participants at risk in Cohorts 2 and 3. No like-for-like control comparison is described. Consequently, differences in observed summaries cannot be interpreted as causal effects of dose or schedule.
More broadly, a study record can communicate the intended question and selected descriptive results while leaving important uncertainty unresolved. Here, the absent primary endpoint result, unreported analysis plan, unexplained cohort risk entries, and lack of reported precision estimates restrict interpretation. The findings should be read as limited registry information about this study, not as a definitive estimate of severe-event frequency, a comparative assessment, or evidence about treatment benefit.
14. Why This Trial Matters Statistically
This trial illustrates why endpoint labels and reported safety summaries must be read carefully. Its primary endpoint is a participant-based measure of severe TEAEs, but the registry’s adverse-event summaries classify serious and other non-serious events. Because severity and seriousness are different concepts, a reader cannot substitute one category for the other. Keeping those definitions separate prevents an apparently relevant safety count from being mistaken for the endpoint result.
It also shows the importance of denominators and analysis populations. The registry gives at-risk counts for the adverse-event summaries, but lists 0 at risk in Cohorts 2 and 3 and does not explain those entries. A percentage such as the 66.7% listed for muscular weakness is difficult to interpret fully when its basis is not reported. Clear denominators and outcome-specific populations are essential for understanding what a proportion represents.
The design matters as well. Nonrandomized cohorts with different regimens do not provide the same basis for comparison as randomized groups. In this record, the adverse-event summary does not support a meaningful comparison across all three regimens. Finally, a study’s stated aims are not equivalent to reported results: the primary endpoint and secondary 6MWT outcome are identified, but their results are not reported in the registry record. These distinctions are useful when evaluating any clinical trial record, especially one with limited enrollment and incomplete outcome reporting.
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 direct limitation is that the primary severe-TEAE result is not reported in the registry record. The record therefore does not provide the endpoint estimate needed to answer the main stated safety question. It also does not report the 6MWT result, despite listing it as a secondary outcome.
The study was open-label and nonrandomized, with cohorts receiving different dosing schedules. No like-for-like control comparison is described. The adverse-event summaries list participants at risk only in Cohort 1; Cohorts 2 and 3 have zero at risk, with no explanation in the record. This prevents a useful safety comparison across the regimens and leaves the reason for those entries unclear.
The serious-event summary lists muscular weakness at 66.7%, but the denominator or calculation basis is not reported. The record does not provide a confidence interval for the primary endpoint, an analysis plan, or a reported inferential analysis. It does not describe missing-data handling, reasons for absent outcomes, or the reason the study was terminated. These are limitations of the information reported in the registry; they do not establish why the information is absent or what unreported analyses may have been conducted.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Study to Evaluate the Safety of AT2220 (Duvoglustat) in Pompe Disease — NCT00688597.
- Registry record last updated 2025-09-11; status last verified 2025-09.
- Results first posted 2018-08-17.
- 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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19. Record Summary
NCT00688597 is a phase 2, open-label, nonrandomized, multicenter study of oral duvoglustat (AT2220) in Pompe disease. It evaluated three dosing regimens and lists severe treatment-emergent adverse events as the primary endpoint. The study status is terminated; the registry reports enrollment of 3.
The adverse-event summary lists serious and other non-serious event counts for Cohort 1, with 0 participants at risk listed for Cohorts 2 and 3. The severe-TEAE primary result and the secondary 6MWT result are not reported in the registry record. Because the cohorts were nonrandomized and the reported adverse-event information is limited, the record does not support a comparative assessment of the regimens.