Safety and Efficacy of Albuterol in Individuals With Late-onset Pompe Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Albuterol in Individuals With Late-onset Pompe Disease (NCT01885936), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events..

2. Clinical Question

The trial was designed to investigate albuterol’s safety and efficacy for motor function in people with late-onset Pompe disease who were receiving enzyme replacement therapy. Its randomized, double-blind, parallel-group design compared albuterol with placebo. The registry record identifies adverse events as the primary outcome, measured through 52 weeks; the listed secondary outcomes concern forced vital capacity and the 6 Minute Walk Test.

The clinical question therefore has distinct safety and efficacy elements. The primary outcome addresses whether participants experienced adverse events, while the study’s stated purpose includes motor function. Forced vital capacity and the 6 Minute Walk Test are listed as secondary outcomes. Numerical results for those secondary outcomes are not reported in the registry record.

3. Trial Design

The registry record describes a randomized, double-blind, parallel-group phase 1/2 study sponsored by Duke University. Its title specifies people with late-onset Pompe disease receiving enzyme replacement therapy. Participants were assigned to albuterol or placebo, and the listed allocation and masking features indicate randomization and double blinding. Enrollment is recorded as 16.

The registry lists the study start as 2013-06 and primary completion as 2016-12-16. Its status is completed. These dates describe the study record and do not, on their own, establish when each participant entered or completed follow-up.

The intervention descriptions outline dose escalation. For albuterol, the listed schedule begins with 4 mg daily for one week, followed by 4 mg BID for the next 5 weeks. If tolerated, the dose is increased to 8 mg each morning and 4 mg each evening for one week, then 8 mg BID for the remainder of the study. The placebo description lists a corresponding capsule schedule. The registry wording for that description is incomplete, so the full placebo schedule is not reported in the registry record.

The primary outcome is the number of participants with adverse events at 52 weeks. Forced vital capacity from pulmonary function tests at 30 weeks and 52 weeks, and change in the 6 Minute Walk Test, are listed as secondary outcomes. The registry lists 3 outcome measures, but only the primary outcome has numerical arm results in the registry record for this analysis.

The posted results give an albuterol arm size of 8 and a placebo comparator arm size of 5. They report 5 participants with the primary outcome in each arm. The reason the arm-specific result counts differ from the overall enrollment listing, and the analysis population used for these results, 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.

Before assignment: Three enrolled participants decided to withdraw due to travel difficulties.

Overall Study

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events., measured over 52 weeks.

The primary endpoint is the number of participants who experienced adverse events during a 52-week timeframe. It is a count of participants with at least one adverse event, rather than a count of every event episode. A participant who experienced more than one event would still contribute as one participant to this endpoint. The registry’s endpoint description does not provide event-level detail or define a severity threshold for inclusion in this overall count.

This endpoint is used to describe safety experience during the study. Counting affected participants gives a direct summary of how many people in each arm had an adverse event, but it does not show the number, type, timing, duration, or severity of events. The separate serious adverse event figures provide information about serious events, but do not replace the broader primary count.

The posted results list 5 participants with adverse events among 8 in the albuterol arm and 5 among 5 in the placebo comparator arm. These are the registry’s participant counts, not a rate per unit of follow-up. The record does not report a confidence interval or an inferential test for the two-arm comparison, and the available information does not establish whether all randomized participants contributed to the endpoint.

Although the study title and summary describe an interest in motor function, the primary endpoint is an adverse-event count. Forced vital capacity and the 6 Minute Walk Test are listed as secondary outcomes. Numerical results for those measures are not reported in the registry record, so the primary count alone cannot describe the trial’s motor-function findings.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is binary at the participant level: each person either experienced an adverse event during the specified timeframe or did not. The registry reports counts rather than a model-based estimate. The albuterol arm lists 5 participants with an event and an arm size of 8; the placebo comparator arm lists 5 participants with an event and an arm size of 5.

What does a binary endpoint represent?

As a general statistical principle, a binary endpoint records whether an outcome occurred for each participant. A group can be summarized by the count with the outcome and the number assessed. That summary is useful for describing the posted data, but a complete comparison usually also describes uncertainty. The registry record does not report a confidence interval or a test for this two-arm outcome.

For a binary endpoint, analysts may compare the probability of an event across groups using measures such as a risk difference, a risk ratio, or an odds ratio. Those are general examples, not analyses reported for this trial. The available record does not provide an estimable two-arm comparison, so no such effect measure should be attributed to the registry result. No recalculated comparison is reported.

Why does uncertainty matter?

As a general explanation, a confidence interval describes a range of effect estimates compatible with the observed data under the assumptions of the statistical method. It communicates precision, which a count alone cannot show. A narrow interval generally indicates greater precision than a wide interval. The registry does not report an interval for this endpoint, so the precision of a comparative effect cannot be read from an interval estimate.

Small groups can make uncertainty especially important. In general, when relatively few participants contribute to a binary endpoint, changing the outcome for one participant can substantially affect the observed group summary. Methods that rely on large-sample approximations may also perform poorly with sparse data. Exact methods are sometimes considered for sparse binary outcomes, but the registry record does not identify an inferential method used for this comparison. It would be inappropriate to present any particular method as the trial’s analysis.

What is the role of randomization?

Randomization is intended, as a general design principle, to make assigned groups comparable on average with respect to measured and unmeasured characteristics. It does not guarantee that two small groups will be identical at baseline. Double blinding is a design feature intended to limit the influence of treatment knowledge on care or assessment. Neither feature supplies the missing statistical estimate, and neither removes the need to report which participants were analyzed and how uncertainty was assessed.

The registry identifies the study as randomized, double-blind, and parallel-group. It does not report the method used to generate the allocation sequence, concealment procedures, or whether masking was maintained. Those details are not reported in the registry record. No additional design procedures should be inferred from the labels alone.

What do the sample-size assumptions describe?

The registry record does not report the trial’s own sample-size justification. A planning illustration based on an observed effect is conceptually different from the planned enrollment rationale: it asks how many participants per arm might be needed under stated assumptions to detect an effect of a specified fraction of the observed effect. The listed assumptions for such an illustration are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustration is not evidence of the trial’s original design or an observed power calculation.

As a general principle, sample-size planning depends on the outcome, target effect, variability or event frequency, significance level, power target, allocation, and analysis method. The registry record does not report the assumptions or justification used to choose the trial enrollment. Any planning illustration based on the observed effect is hypothetical and should not be treated as the trial’s design rationale or as proof that the study could detect a particular effect.

What can be concluded from the posted counts?

The counts describe the participants recorded with the endpoint in each arm. They do not provide an adjusted estimate, account for potential missing outcomes, or quantify uncertainty in a comparative effect. The registry record lists no analysis for the two-arm binary comparison and marks the comparison as not estimable from the posted results. Thus the defensible statistical interpretation remains descriptive, rather than a claim of a statistically established difference or absence of difference.

The sponsor’s own analysis would take precedence over a simple unadjusted recalculation if the two conflicted. The record does not identify a sponsor analysis for this comparison, and the stated discrepancy indicator is false. That does not create an inferential result where none is reported; the primary counts remain the available numerical evidence for the endpoint.

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("Albuterol", "Placebo Comparator")
n      <- c(8, 5)
events <- c(5, 5)
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  Albuterol  8  5  62.5  24.5  91.5  30.6  86.3  29.9  86.3
ARM  Placebo Comparator  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes: change in forced vital capacity from pulmonary function tests at 30 weeks and 52 weeks, and change in the 6 Minute Walk Test. It also lists 3 outcome measures. The registry record does not report a multiplicity strategy, such as whether secondary outcomes were considered confirmatory, how testing across outcomes or timepoints was handled, or whether any adjustment was planned. No conclusion about the trial’s control of multiple testing can be drawn without those details.

Numerical secondary-outcome results are not reported in the registry record for this analysis. The listed outcome names alone cannot establish the direction, size, or precision of any motor-function or pulmonary-function result. The record also does not report whether additional outcomes were assessed but not posted.

The analysis population for the primary endpoint is not reported in the registry record. Although overall enrollment is listed as 16, the posted arm sizes are 8 for albuterol and 5 for placebo. The record does not explain how these figures relate, whether all randomized participants were included in the outcome analysis, or whether participants were analyzed according to their assigned groups.

Methods for missing data, withdrawals, exclusions, and incomplete follow-up are not reported in the registry record. Nor are the handling of deviations from the assigned intervention, endpoint adjudication procedures, or a statistical analysis plan. These omissions limit interpretation of how the posted counts were formed and whether they represent all randomized participants at the stated timeframe.

Interim analyses and stopping rules are not reported in the registry record. No assumptions about their presence or absence should be made. Without a stated analysis plan and details of the outcome population, the posted counts should be treated as the registry’s descriptive results, not as a fully documented confirmatory analysis.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 0 participants with serious adverse events in the albuterol arm and 0 in the placebo comparator arm. It also lists 0 deaths in each arm. These are counts in the posted safety record; they do not indicate that no adverse events of any kind occurred.

The broader primary endpoint counts participants with adverse events, and the arm results list 5 participants in each group. The separate safety details list 5 participants with other adverse events among 8 at risk in the albuterol arm and 5 among 5 at risk in the placebo comparator arm. The serious-event counts are therefore distinct from the broader adverse-event counts. The registry provides no serious adverse event terms in its listed top serious terms.

These figures count affected participants, not the total number of event episodes. They do not describe the event types, severity beyond the serious classification, onset, duration, recurrence, or relationship to study treatment. Zero reported serious events is a count, not proof that a treatment has no serious risks. With the arm sizes listed in the record and no inferential comparison, the figures should be read as descriptive safety data rather than a precise comparative estimate.

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

The primary endpoint offers a limited but direct description of the safety outcome recorded in the registry: 5 participants in the albuterol arm and 5 in the placebo comparator arm experienced adverse events. The arm sizes listed are 8 and 5, respectively, and the outcome timeframe is 52 weeks. The registry separately lists 0 serious adverse events and 0 deaths in each arm.

Those counts do not establish that the interventions have the same safety profile or that one has a different profile. A statistical comparison, with an estimate of uncertainty, is not reported and is not estimable from the posted result as recorded. In general, lack of a reported statistically significant difference is not the same as evidence of equivalence; in this case, there is no reported inferential test to interpret. The counts also cannot describe event severity, clinical importance, or causation.

The study’s stated purpose includes evaluating motor function, but its primary endpoint is the number of participants with adverse events. Forced vital capacity and the 6 Minute Walk Test are listed as secondary outcomes. Their numerical results are not reported in the registry record. Accordingly, the posted primary result does not answer whether motor function changed or whether any change differed between the groups.

The study is recorded as completed, and its design is listed as randomized, double-blind, and parallel-group. These are important design descriptors, but the record does not provide enough detail to assess every aspect of implementation or analysis. In particular, the relationship between overall enrollment and the posted arm sizes, the analysis population, and methods for missing outcomes are not reported.

The result therefore supports a narrow conclusion: the registry reports participant counts for adverse events and serious events in the two listed arms. It does not provide a precise comparative estimate, an efficacy result for the listed functional outcomes, or enough event detail to characterize the safety experience comprehensively. No stronger conclusion should be drawn from these counts alone.

14. Why This Trial Matters Statistically

This trial illustrates why a study’s stated clinical aim and its registered primary endpoint need to be read separately. The title and summary describe an investigation of albuterol’s safety and efficacy for motor function in people with late-onset Pompe disease receiving enzyme replacement therapy. The primary outcome, however, counts participants with adverse events. Forced vital capacity and the 6 Minute Walk Test are listed as secondary outcomes. Without numerical results for those secondary measures, the posted primary result cannot answer the motor-function question by itself.

It also shows the difference between a descriptive result and an inferential comparison. The registry gives participant counts in both arms, but reports no estimable two-arm statistical comparison. Counts alone do not communicate how precisely an underlying between-group effect has been estimated. This distinction matters particularly when the listed arm sizes are small and uncertainty may be substantial.

The record further demonstrates why reporting the analysis population and missing-data procedures is important. Overall enrollment is listed as 16, while the arm-specific results list sizes of 8 and 5. The record does not explain the relationship between those entries. Without that explanation, readers cannot determine from the record alone how the posted endpoint population relates to the full enrollment.

Finally, planning illustrations based on an observed effect are not substitutes for a trial’s original sample-size rationale. They answer a hypothetical planning question under explicit assumptions, not whether the completed study was designed around those assumptions. Separating design rationale, observed outcomes, and post hoc planning helps keep statistical interpretation aligned with what the registry actually documents.

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 main limitation for interpreting the primary result is the absence of a reported inferential comparison. The registry lists adverse-event counts but does not provide a confidence interval, p-value, or other comparative estimate, and the two-arm binary comparison is not estimable from the posted results. The figures therefore describe what was recorded without quantifying uncertainty about a group difference.

There is also an unresolved difference between the overall enrollment listing of 16 and the arm-specific result sizes of 8 and 5. The registry record does not explain the analysis population, exclusions, withdrawals, or missing outcomes. It is not possible to determine from these entries whether the endpoint counts include all randomized participants or what follow-up information was available for each person.

The safety detail is limited to counts. Event types, event timing, duration, severity beyond the serious classification, and treatment relatedness are not reported in the registry record. The absence of listed serious events or deaths does not provide information about less serious events beyond the broad counts, nor does it describe the clinical context of any event.

The study’s stated interest in motor function is not accompanied by numerical secondary-outcome results in the record used for this analysis. Forced vital capacity and the 6 Minute Walk Test are listed, but their results and associated uncertainty are not reported. The available primary outcome therefore cannot resolve the efficacy question described in the study title.

Further limitations include the lack of a reported sample-size rationale, statistical analysis plan, multiplicity approach, missing-data method, interim-analysis details, and stopping rules. These items are not reported in the registry record. The design labels of randomization and double blinding do not fill in those methodological details. Conclusions should remain confined to the descriptive participant counts that are posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy of Albuterol in Individuals With Late-onset Pompe Disease — NCT01885936.
• Registry record last updated 2019-07-15; status last verified 2019-07.
• Results first posted 2018-02-06.
• 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

NCT01885936 is a completed, randomized, double-blind, parallel-group phase 1/2 study sponsored by Duke University. It concerns albuterol versus placebo in people with late-onset Pompe disease receiving enzyme replacement therapy. The registry lists enrollment of 16, a study start of 2013-06, and primary completion on 2016-12-16.

The primary outcome is the number of participants with adverse events at 52 weeks. The posted results list 5 participants with events in the albuterol arm, with an arm size of 8, and 5 in the placebo comparator arm, with an arm size of 5. Serious adverse events and deaths are listed as 0 in both arms. A two-arm statistical comparison is not reported as estimable.

Forced vital capacity and the 6 Minute Walk Test are listed as secondary outcomes, but numerical results are not reported in the registry record. The analysis population, missing-data procedures, multiplicity approach, and trial sample-size rationale are also not reported. The primary result is therefore descriptive and does not establish a comparative safety effect or answer the listed motor-function question.