Safety/Tolerability/Pharmacokinetic (PK)/Pharmacodynamics (PD) Study of BMN701 in Patients With Late-Onset Pompe Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety/Tolerability/Pharmacokinetic (PK)/Pharmacodynamics (PD) Study of BMN701 in Patients With Late-Onset Pompe Disease (NCT01230801), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

These features define the scope of interpretation. The registry record gives counts for the listed dose groups and a total, but it does not provide a randomized comparison or a control group against which to estimate what would have happened without BMN 701. The adverse-event counts can describe what was recorded among participants in this study; by themselves, they cannot distinguish effects of treatment from the underlying disease, other influences, or chance variation.

3. Trial Design

This was a completed phase 1/2, open-label, multicenter study of BMN 701 in patients with late-onset Pompe disease. The registry record describes a single-group, multiple dose escalation design. The brief summary states that BMN 701 was administered by intravenous infusion every 2 weeks over a 24-week treatment period. The primary outcome timeframe is also 24 weeks.

The record lists 22 participants enrolled and describes three dose groups: BMN 701 5 mg/kg, BMN 701 10 mg/kg, and BMN 701 20 mg/kg. The group counts in the adverse-event results are 3, 3, and 16 participants, respectively. The registry does not report how participants came to receive each dose, whether dose escalation followed a specified rule, or whether participants moved between dose groups. Those details should not be inferred from the group labels alone.

The study is not described as a randomized controlled trial. Allocation is recorded as not applicable, masking is absent, and the model is single-group. Accordingly, the dose groups should be read as descriptive groups within the study, not as equivalent treatment and control arms. Any differences in their observed event counts could reflect the differing group sizes or other differences that the registry record does not describe.

The registry record gives a start date of 2011-01-17, a primary completion date of 2013-03-06, and a completed status. BioMarin Pharmaceutical is listed as the sponsor. The study title and summary indicate that safety and tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy were among its interests. However, the primary outcome reported in the record is the number of participants with adverse events. The results for other outcomes and the details of the study’s statistical plan 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

Analysis population for the primary outcome, as defined in the registry: Safety 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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over 24 weeks.

The primary endpoint is the number of participants with adverse events, measured as a count of participants in the safety population over 24 weeks. It asks whether each participant was reported as having an adverse event during the specified period, rather than measuring the total number of separate events or the average severity of events. The registry record describes the outcome as a measure of safety and tolerability.

A participant count is useful for a safety summary because it conveys how many people in the study experienced a recorded event. It is distinct from an event count: one person could potentially have more than one event, but the primary outcome is expressed in participants, not repeated event totals. The record also reports serious adverse-event counts and other adverse-event counts; these should not be conflated with the primary endpoint unless the record explicitly defines them as the same measure.

Because the study has no control group, the endpoint describes events observed during treatment rather than estimating an excess attributable to treatment. The count also does not, on its own, convey when events occurred, how long they lasted, whether they led to stopping treatment, or how they were judged in relation to treatment. Those details are not reported in the registry record. A separate secondary outcome, change from baseline in the Six Minutes Walk Test, is listed, but its result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event summarized as a count: a participant is counted as having an adverse event or not having one during the stated timeframe. The registry presents participant counts rather than an event rate per unit of follow-up. This makes the outcome straightforward to describe, but it does not preserve information about how many events each participant had or precisely when they occurred.

What does a participant count communicate?

A count communicates the number of people recorded in an outcome category. It is not the same as a count of all event episodes. For example, multiple events in one participant would still concern one participant in an outcome defined as the number of participants with adverse events. The registry reports the primary endpoint in the safety population, and its description specifies a 24-week timeframe. It does not report additional detail about event ascertainment, follow-up completeness, or how a participant was handled if their observation period differed from that timeframe.

General statistical explanation: a binary outcome can also be expressed as a proportion, and uncertainty around a proportion can be represented by a confidence interval. A confidence interval describes a range of values compatible with the data under a specified statistical method; it is not a guarantee that the true value lies in that range. No confidence interval for the primary endpoint is reported in the registry record. No new proportions or interval estimates are calculated in this interpretation.

Why does the design matter for comparisons?

The registry classifies the study as single-group, open-label, and without masking. Allocation is recorded as not applicable. As a result, the group counts are descriptive rather than the result of a randomized comparison. General statistical explanation: random allocation, when used, can help balance measured and unmeasured characteristics between groups on average. Without it, differences between groups may reflect who was in each group, how groups were formed, or other influences, as well as any treatment-related differences. The registry record does not report the process used to assign participants to the dose groups.

The dose groups also have different sizes: 3 participants at 5 mg/kg, 3 at 10 mg/kg, and 16 at 20 mg/kg. A count from a group with few participants is inherently limited in how much information it provides about the range of outcomes that might occur in a larger population. General statistical explanation: random variation can have a larger effect on observed proportions in smaller samples. The registry record provides no comparative model or inferential analysis to account for group size or other differences.

What can and cannot be concluded from statistical testing?

The registry record reports 0 outcome analyses. It does not report p-values, confidence intervals, a model-based estimate, or an adjusted comparison for the primary endpoint. Therefore, there is no posted inferential test establishing a difference between dose groups. A difference in observed counts alone is not a statistical test and does not show that an underlying difference is unlikely to be due to chance.

General statistical explanation: a p-value, when calculated under a defined model and null hypothesis, describes how incompatible the observed data are with that hypothesis; it does not measure the probability that the hypothesis is true or the size of a treatment effect. A confidence interval complements an estimate by communicating its precision. Neither should be interpreted without attention to the design and the assumptions of the analysis. No such inferential results are reported for these safety counts.

How should the planning illustrations be understood?

The planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed or conducted as a two-arm randomized comparison. The study itself is recorded as single-group, and its dose groups are not identified as like-for-like controls.

General statistical explanation: sample-size calculations ask how many participants a future design might require to detect a specified effect under stated assumptions. Their outputs depend on the assumed effect, variability or event frequency, significance level, power target, allocation, and analysis method. A planning calculation based on an observed effect does not establish that the original study had adequate power, nor does it describe the probability that the study’s result is correct. The planning illustrations are not observed power. The registry record does not report a protocol-based sample-size justification or enough detail to determine whether the illustration matches the study’s design.

General statistical explanation: over-dispersion matters when count data vary more than a chosen model expects, because a model that understates variability can produce overly narrow uncertainty intervals or misleading tests. This endpoint is a participant count for a binary event, not a reported recurrent-event rate. The registry record does not report a model for over-dispersion, repeated-event analysis, or any other statistical model for the posted safety counts. Such methods should not be attributed to the study without documentation.

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("BMN 701 5 mg/kg", "BMN 701 10 mg/kg", "BMN 701 20 mg/kg")
n      <- c(3, 3, 16)
events <- c(3, 3, 15)
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  BMN 701 5 mg/kg  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  BMN 701 10 mg/kg  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  BMN 701 20 mg/kg  16  15  93.8  69.8  99.8  71.7  98.9  71.3  98.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 7 outcome measures and identifies the number of participants with adverse events as the primary outcome. Change from baseline in the Six Minutes Walk Test is listed as a secondary outcome. Although the study title and summary refer to pharmacokinetics, pharmacodynamics, and preliminary efficacy, results for those outcomes are not reported in the registry record. The record reports 0 outcome analyses.

Multiplicity arises when several outcomes, timepoints, groups, or analyses are examined. General statistical explanation: when many statistical tests are performed, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for multiple testing. The registry record does not report whether multiplicity was addressed, how outcomes were prioritized beyond the primary designation, or whether there were interim analyses. No adjustment strategy should be inferred.

The record names the safety population for the primary outcome, but does not report its detailed definition or how participants were included in it. It does not report how missing observations, withdrawals, incomplete follow-up, or deviations from the treatment schedule were handled. Imputation methods, rules for censoring or excluding observations, and sensitivity analyses are not reported in the registry record.

These omissions matter because event counts depend on how outcomes and observation periods are defined and on whether follow-up is complete. The registry record gives no basis for assessing whether missing data could have affected the counts. The reported results should therefore be understood as the posted counts in the stated population and timeframe, without assuming an unreported missing-data method or statistical adjustment.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypersensitivity (6.2%), hypoglycaemia (6.2%), aggression (6.2%), hypertensive crisis (6.2%).

The serious adverse-event counts are 0 participants in the BMN 701 5 mg/kg group, 0 in the BMN 701 10 mg/kg group, and 4 in the BMN 701 20 mg/kg group. The total is 4 participants among 22. The record reports no deaths. These are participant counts, not totals of every serious event episode.

For other adverse events, the record reports 3 participants in each of the 5 mg/kg and 10 mg/kg groups, and 15 in the 20 mg/kg group; the total is 21. The terms listed among the top serious events are Hypersensitivity, Hypoglycaemia, Aggression, and Hypertensive crisis, each reported at 6.2%. The registry record does not provide enough information to assign those terms to particular dose groups or to determine whether they occurred in the same or different participants.

General statistical explanation: an observed count does not indicate how precisely the underlying frequency is known. This is especially important when group sizes are small. The registry record does not report confidence intervals or a comparative safety analysis. The counts describe events recorded during the study; they do not by themselves establish cause, comparative risk, or the frequency expected outside this study.

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

The posted results describe adverse events recorded among participants with late-onset Pompe disease who received BMN 701 in this open-label phase 1/2 study. They show that 4 participants had serious adverse events, 21 had other adverse events, and no deaths were reported. The counts are presented for the study’s safety population and the primary outcome timeframe of 24 weeks. They are useful as a factual account of the recorded safety experience in this study.

They do not establish that BMN 701 caused each event. A single-group study has no concurrent control group to help separate events associated with study treatment from events that might occur because of the condition, other circumstances, or chance. Open-label conduct also means the study was not masked, although the registry record does not describe how this affected event reporting or assessment.

The counts do not show how frequently events occurred over different lengths of follow-up, how many separate events each person experienced, how serious events were managed, or whether they affected treatment continuation. Those details are not reported in the registry record. The listed serious-event terms and their reported percentages do not establish a dose-specific pattern or show whether terms overlapped within participants.

The results also do not establish a comparative safety difference among dose groups. The groups are unequal in size, and the record does not identify randomized allocation or report a statistical comparison. Counts across these groups are therefore descriptive, not a controlled estimate of the effect of one dose relative to another.

Finally, the listed secondary Six Minutes Walk Test outcome does not have a result reported in the registry record. The record also does not report results for pharmacokinetic, pharmacodynamic, or preliminary efficacy outcomes mentioned in the study title and summary. The safety data should not be used to infer those outcomes. They characterize the events recorded during this study, with the uncertainty and design limitations.

14. Why This Trial Matters Statistically

This study illustrates how the design determines what a safety result can answer. A single-group dose escalation study can record adverse events among people exposed to the study product and describe counts by dose group. Without a control group, however, the result does not directly estimate how those counts compare with an alternative treatment or with no study treatment. The distinction between describing events and estimating a treatment effect is central to interpreting clinical trial data.

The outcome is a participant count, which is clinically legible but statistically limited when presented without interval estimates or an analysis plan. A count tells readers how many participants were recorded in a category, but does not communicate its precision. The smaller dose groups contain 3 participants each, while the 20 mg/kg group contains 16. These group sizes make it particularly important not to treat raw count differences as proof of a dose effect.

The record also shows why outcome availability matters. The study is described as addressing safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy, and it lists 7 outcome measures. Yet the registry record reports 0 outcome analyses and does not report results for the listed secondary Six Minutes Walk Test outcome. Readers should distinguish the broad aims of a study from the results actually posted for individual outcomes.

Finally, the planning assumptions associated with sample-size illustrations are not interchangeable with a trial’s design or with observed evidence. The listed assumptions use a two-arm framework, whereas the study is recorded as single-group and its dose groups are not like-for-like controls. Recognizing that mismatch helps prevent a planning exercise from being mistaken for a randomized comparison or a conclusion about the study’s power.

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 registry record gives a limited account of the safety results. It reports participant counts by dose group and in total, but no confidence intervals, p-values, or inferential analysis. As a result, the precision of the counts is not quantified, and no statistical comparison between dose groups is available.

The study is open-label and single-group, with no control group identified. Allocation is recorded as not applicable. The registry record does not report how dose assignment occurred, whether participants changed dose, or whether groups differed in characteristics that could influence observed events. The three groups also have different sizes, limiting direct interpretation of count differences.

Details of adverse-event collection and classification are not reported in the registry record. The record does not explain how seriousness was assessed, how events were attributed, how long individual participants were followed, or whether all participants completed the 24-week period. It also does not report missing-data handling, treatment discontinuations, or sensitivity analyses. These omissions limit assessment of completeness and interpretation of the recorded counts.

The registry lists serious-event terms with a reported value of 6.2% for each term but does not provide the underlying participant-level detail needed to understand overlap or dose distribution. No results are reported for the listed secondary Six Minutes Walk Test outcome or the pharmacokinetic, pharmacodynamic, and preliminary efficacy topics named in the study description. Finally, the protocol’s statistical analysis plan, multiplicity approach, interim analyses, and sample-size justification are not reported in the registry record. The posted safety counts should be interpreted within these limits.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety/Tolerability/Pharmacokinetic (PK)/Pharmacodynamics (PD) Study of BMN701 in Patients With Late-Onset Pompe Disease — NCT01230801.
• Registry record last updated 2018-06-11; status last verified 2018-05.
• Results first posted 2018-06-11.
• 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

The registry record describes a completed phase 1/2, open-label, multicenter, single-group dose escalation study of BMN 701 in patients with late-onset Pompe disease. The brief summary describes intravenous infusions every 2 weeks over a 24-week treatment period. The primary outcome is the number of participants with adverse events in the safety population over 24 weeks.

The record lists 22 participants and three dose groups: 5 mg/kg, 10 mg/kg, and 20 mg/kg. It reports 4 participants with serious adverse events, 21 with other adverse events, and no deaths. It also lists a change from baseline in the Six Minutes Walk Test as a secondary outcome, but its result is not reported in the registry record.

There is no control group, and the record reports 0 outcome analyses. The safety findings are descriptive counts, not a randomized estimate of treatment effect. Statistical analyses, missing-data methods, and the protocol’s sample-size justification are not reported in the registry record.