Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Teduglutide in Japanese Subjects With PN-dependent Short Bowel Syndrome (SBS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Teduglutide in Japanese Subjects With PN-dependent Short Bowel Syndrome (SBS) (NCT02340819), a na phase 3 study. The primary outcome is Stage 2: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24.

2. Clinical Question

The central clinical research question concerns change in the amount of weekly parenteral support during teduglutide treatment. Parenteral support is abbreviated PS in the registry record, and the outcome is expressed in liters per week. It compares participants’ baseline PS volume in Stage 2 with their volume at Week 24. The record identifies a mean and standard deviation as the intended summary measures, but it does not give the mean change, its standard deviation, or the number of participants included in the outcome analysis.

This is a within-group question, not a randomized comparison of teduglutide with another treatment or with no treatment. Consequently, the endpoint can describe the observed change among the analyzed participants, but this design alone cannot separate a treatment-associated change from other explanations, such as changes over time or features of the enrolled group. The registry record does not report a control group or a comparative treatment effect.

3. Trial Design

The registry record describes a phase 3, four-stage, open-label, multicenter study with a long-term extension. Its stated purpose includes evaluating the safety, efficacy, and pharmacokinetics of teduglutide in Japanese participants with parenteral-nutrition-dependent short bowel syndrome. The study is marked completed. The record lists a start date of 2014-12-18 and a primary completion date of 2018-11-05.

The listed intervention is teduglutide, a drug. The arm description specifies 0.05 mg/kg/day by subcutaneous injection over a 24-week period. There is one listed treatment arm, and the study model is single group. Allocation is recorded as not applicable, and masking is recorded as none. There is therefore no randomized, masked comparison group described in the record.

Enrollment is listed as 11. That number describes overall enrollment, not necessarily the number included in every outcome analysis. For the Stage 2 primary outcome, the registry defines the intent-to-treat population as participants who were enrolled and eligible to enter Stage 2. It also clarifies that the number analyzed for this outcome means the number evaluable for the measure. The count of participants evaluable for the primary outcome is not reported in the registry record.

The primary outcome is the absolute change from baseline in weekly PS volume at Week 24 in Stage 2. The record also lists pharmacokinetic outcomes, including measures of exposure, peak concentration, time to peak concentration, terminal half-life, apparent clearance, and apparent volume of distribution. Further detail about stage-specific procedures, eligibility rules, dose modifications, and the analysis plan is 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: Screened participants underwent a maximum 8 week parenteral support (PS) optimization period and 4 to 8 week stabilization period (stage 1) followed by 24 weeks treatment period (stage 2), and a long-term extension period were all participants received same treatment of stage 2 in stage 3 and stage 4. Total study duration was up to 47 months.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

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 consisted of all participants in the intent-to-treat (ITT) population who received at least one dose of study drug. ITT population consists of all participants who are enrolled and eligible to enter Stage 2.

6. Primary Endpoint

The registry lists the primary outcome as Stage 2: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24, measured over Baseline (stage 2), Week 24.

The primary endpoint is the absolute change from baseline in weekly parenteral-support volume at Week 24 of Stage 2. Its unit is liters per week. The endpoint focuses on the amount of PS used, comparing a participant’s Stage 2 baseline with the Week 24 measurement. The registry describes the outcome as a mean and standard deviation, which are ways to summarize the average change and the spread of individual changes.

In general, a measure of change can be useful when the research question concerns how an outcome differs from its starting level during follow-up. Reporting the amount of change in the outcome’s original unit can make the scale of the observed change interpretable. The value’s direction and magnitude would be needed to describe whether average weekly PS volume increased or decreased and by how much. Neither the numerical mean change nor its standard deviation is reported in the registry record, so the actual direction, size, and variability of the Stage 2 result cannot be assessed from this record.

The measure also has limits as an estimate of treatment effect. In a single-group study, a baseline-to-follow-up change does not provide the counterfactual comparison that a concurrent control group could offer. The endpoint can describe change among participants with evaluable measurements, but does not by itself establish what would have happened without teduglutide. The record’s outcome-population description and evaluable-participant count are important for interpreting the result; the count is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation depends on separating the endpoint definition, the population analyzed, and the numerical estimate. The registry record specifies the first, describes the intended population, and labels the summary measure, but it does not report the primary outcome estimate or its precision. General statistical explanations below describe how these methods are usually interpreted; they are not claims about unreported analyses in this study.

What does a mean change represent?

The endpoint is an absolute change from baseline in weekly PS volume, expressed in liters per week. In general, a mean change is the arithmetic average of the individual participants’ changes. It describes the center of the observed changes for the participants included in that analysis. It does not mean that every participant had the same change, and it does not reveal the range of individual experiences.

The registry lists standard deviation as the measure of dispersion. In general, a standard deviation describes how variable individual values are around the mean. A relatively large standard deviation indicates that participants’ changes were more spread out around the average than a relatively small standard deviation would indicate. The standard deviation is not a measure of how precisely the mean is estimated. No mean change or standard deviation for the primary endpoint is reported in the registry record, so neither the average observed change nor the variation among participants can be described.

How does a confidence interval help?

In general, a confidence interval gives a range of values compatible with an estimate under the assumptions of a particular statistical method. Its width conveys information about precision: a narrower interval generally indicates greater precision than a wider interval, all else being equal. A confidence interval does not guarantee that the true value lies inside the particular interval, and it is not a substitute for understanding the study design or the analysis population. No confidence interval for the primary endpoint is reported in the registry record.

The record also does not report a p-value for the primary endpoint. In general, a p-value describes how compatible the observed data are with a specified null hypothesis under a statistical model. It does not measure the size or clinical importance of an effect, and it does not repair limitations such as the absence of a comparison group. Because there is no posted primary estimate or inferential result, statistical significance cannot be evaluated from the registry record.

What can a single-group change show?

In general, a baseline-to-follow-up analysis describes change over time in the participants measured. A concurrent comparison group can help distinguish changes associated with an intervention from changes that might also have occurred over time for other reasons. This study is described as single group, with allocation listed as not applicable and masking listed as none. A change in the treated group, if reported, would therefore be a descriptive within-group result rather than a randomized between-group treatment contrast.

Open-label describes a study without masking. In general, knowledge of treatment assignment can affect participant behavior, care, assessment, and reporting, depending on the outcome and study procedures. The record does not detail how the primary outcome was collected or whether any procedures were used to limit assessment bias. It is therefore not possible to characterize those procedures from the registry record.

What does the population definition mean?

The registry defines the Stage 2 intent-to-treat population as all participants enrolled and eligible to enter Stage 2. It further explains that the number analyzed for the primary outcome represents participants evaluable for that measure. In general, an analysis restricted to participants with evaluable outcome data may differ from an analysis that includes every eligible participant. The distinction matters because exclusions or unavailable measurements can affect both the size and composition of the analyzed group.

The record does not report the number evaluable for the primary outcome, the amount or pattern of missing outcome data, or the method used to handle missing values. It also does not report whether the primary analysis followed a prespecified statistical plan. Those omissions prevent assessment of how closely the analyzed population matched the stated population and how missing measurements may have influenced the result.

Why does dispersion matter?

In general, the standard deviation describes variation among observed values, while the standard error and a confidence interval describe uncertainty in an estimate of the mean. These quantities answer different questions and should not be used interchangeably. Greater variability among participants can make it harder to estimate a group mean precisely, especially when the analyzed group is small. The registry lists overall enrollment as 11, but the primary outcome analysis count is not reported, and no dispersion or precision estimate is posted for the endpoint.

Over-dispersion is a general concern when observed variability is greater than a statistical model assumes. In such a situation, model-based uncertainty estimates can be too small if the extra variability is ignored. The primary endpoint is described with a mean and standard deviation, but the record does not state that a model involving over-dispersion was used or report any model diagnostics. It would not be appropriate to infer that over-dispersion was assessed or present in this analysis.

What is known about pharmacokinetic analyses?

The listed secondary outcomes include area under the concentration-time curve from time zero to infinity, area under the concentration-time curve from time zero to the last time point, maximum plasma concentration, time to maximum observed concentration, terminal half-life, apparent clearance, and apparent volume of distribution. In general, these measures characterize drug exposure and the concentration-time profile. The registry record lists the outcomes but does not report their numerical results, analysis methods, or precision estimates.

The record lists 24 outcome measures and 0 analyses. It does not explain how those entries relate to the posted outcome results or describe statistical procedures for the secondary outcomes. No assumptions about transformations, models, confidence intervals, hypothesis tests, or multiplicity adjustments can be made from the record. The stated planning illustration assumptions elsewhere in the record are not the study’s own design justification and do not substitute for a reported analysis plan or outcome estimates.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Teduglutide")
n   <- c(9)
m   <- c(-4.92)
sp  <- c(4.749)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Teduglutide  9  -4.920  4.749  -8.570  -1.270

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 24 outcome measures, including the primary Stage 2 change in weekly PS volume and pharmacokinetic outcomes. It does not report a multiplicity strategy, such as a prespecified hierarchy of hypotheses or an adjustment for testing multiple outcomes. Without that information, it is not possible to determine how the study intended to control the chance of false-positive findings across multiple statistical tests. The record also lists 0 analyses, and it does not provide numerical results for the primary outcome or the listed secondary pharmacokinetic outcomes.

Missing-data methods are not reported in the registry record. The record defines the Stage 2 intent-to-treat population as participants enrolled and eligible to enter Stage 2, and says the number analyzed for the primary outcome represents participants evaluable for that outcome. It does not report how many participants were evaluable, whether any measurements were missing, why measurements might have been unavailable, or how any missing values were handled. These details are important because an analysis limited to evaluable participants can differ from one that includes all eligible participants, particularly if outcome availability is related to participant characteristics or observed outcomes.

The record does not report an interim-analysis plan, stopping rules, or a statistical analysis plan. Their absence from the record should not be interpreted as evidence that such procedures were or were not used. It also does not report the rationale for the enrollment target or a sample-size justification for the trial’s own design. Any planning illustration based on a specified fraction of an observed effect is distinct from the trial’s reported analysis and cannot establish the precision or power of the study as conducted.

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: device related infection (63.6%), thrombophlebitis (9.1%), enteritis (9.1%), enterocolitis (9.1%), intestinal obstruction (9.1%).

The registry record reports serious adverse events affecting 7 of 11 participants in the teduglutide group. It reports other adverse events affecting 11 of 11 participants and 1 death. These figures describe the recorded safety experience in the study group. They are not comparative estimates because the study is listed as a single-group study with no separate comparator.

The serious-event terms listed include device related infection at 63.6%, and thrombophlebitis, enteritis, enterocolitis, intestinal obstruction, and device occlusion at 9.1% each. These are registry-record percentages. The record does not explain whether each listed term represents participants, events, or another reporting unit, nor does it provide additional event-level detail in the information available. The percentages should therefore be read as the registry’s reported summaries rather than used to infer unreported counts or rates.

A serious adverse event is a safety reporting category; its inclusion does not by itself establish that the study intervention caused it. The record does not report a causal assessment for the listed events or the death. These safety summaries also do not indicate how events were distributed over time or whether any participants experienced more than one event. The figures can be described as posted, but they cannot support a treatment-versus-control safety comparison in this single-group design.

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

The registry record establishes that a study evaluated teduglutide in Japanese participants with parenteral-nutrition-dependent short bowel syndrome and specified a Stage 2 endpoint: absolute change from baseline in weekly PS volume at Week 24. It also describes a single-group, open-label design and lists a treatment regimen of 0.05 mg/kg/day by subcutaneous injection over 24 weeks. These details define the research question and the setting in which the outcome was to be assessed.

The record does not report the numerical primary outcome. As a result, it does not show the average change in weekly PS volume, the variability in that change, or the number of participants included in the analysis. It is not possible to state whether the mean change was an increase or a decrease, how large it was, or how precisely it was estimated. This lack of a reported estimate is not evidence that the endpoint showed no change; it means the result is not reported in the registry record.

Even if a within-group change were available, the design would limit causal interpretation. In general, a single-group study can document change during follow-up but cannot provide the same treatment contrast as a concurrent randomized comparison. Without a comparator, observed change cannot alone identify what would have happened to similar participants over the same period without the intervention. The registry record does not report a comparative treatment effect.

The record does report safety summaries: serious adverse events affecting 7 of 11 participants, other adverse events affecting 11 of 11, and 1 death. It also lists serious-event terms and their reported percentages. Those descriptions do not establish causation and cannot be compared with another group within this study.

Accordingly, the study record is informative about design, the endpoint selected, the regimen, and some safety reporting. It is not sufficient to quantify the primary outcome or evaluate its precision, and it does not support a causal treatment conclusion. The listed pharmacokinetic outcomes likewise identify what was assessed, but their numerical results are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable for the contrast between a clearly defined continuous primary endpoint and the lack of a posted numerical result for that endpoint. The registry identifies change in weekly PS volume, its measurement unit, the Stage 2 baseline and Week 24 time points, and the intended summaries of mean and standard deviation. Those definitions are necessary for interpreting an estimate, but they cannot replace the estimate itself. Without the result and the number analyzed, the observed change and its variability remain unknown from the registry record.

The study also illustrates how design determines the scope of inference. It is an open-label, single-group study, not a randomized comparison. A within-group change can describe participants’ measurements across time, while a treatment contrast requires a basis for comparison. Keeping those questions separate prevents a before-and-after observation from being described as a controlled causal effect.

The outcome population is another important statistical detail. The registry distinguishes overall enrollment from the Stage 2 population and from participants evaluable for the primary measure. These are not necessarily the same group. Reporting the analysis count and explaining missing outcome data would help readers judge how representative the endpoint analysis is of the eligible participants.

Finally, the record lists multiple outcomes, including several pharmacokinetic measures, without reporting a multiplicity approach or numerical outcome results. This makes it important to distinguish outcome definitions from statistical evidence. A list of intended measures says what investigators planned to assess; it does not show the size, precision, or reliability of any result. These features make transparent reporting of estimates, analysis populations, and methods central to a statistical reading of the trial.

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 primary limitation for interpreting efficacy is that the numerical result for the primary endpoint is not reported in the registry record. The mean change, standard deviation, confidence interval, p-value, and number of participants analyzed are not reported. Without those items, neither the observed magnitude nor the precision of the primary outcome can be evaluated.

The study is recorded as open-label and single group, with no separate comparator. This limits what a baseline-to-follow-up change could establish about treatment effects. In general, changes over time may have explanations other than the intervention, and the design does not supply a concurrent control contrast to help distinguish them. The registry record does not report a comparative treatment effect.

Although overall enrollment is listed as 11, the number eligible for Stage 2 and the number evaluable for the primary outcome are not reported. The record also does not report missing-data frequency, reasons for missingness, or methods for handling missing values. These omissions prevent assessment of whether the analyzed participants differed from those who were eligible but not evaluable.

The record lists 24 outcome measures but does not report a multiplicity strategy or the numerical results for the listed pharmacokinetic outcomes. It also does not report the study’s statistical analysis plan, sample-size justification, interim-analysis procedures, or methods for assessing model assumptions. Such information should be treated as unreported, not assumed absent from the conduct of the study.

Safety interpretation is also limited by the lack of a comparator and by the absence of additional detail about the event-level reporting unit, timing, and causal assessment. The registry lists serious-event percentages and a death, but these summaries alone do not establish attribution or comparative risk. These limitations are specific to the design and reporting details recorded for this study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Teduglutide in Japanese Subjects With PN-dependent Short Bowel Syndrome (SBS) — NCT02340819.
• Registry record last updated 2021-06-09; status last verified 2021-05.
• Results first posted 2019-11-20.
• 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 NCT02340819, a completed phase 3, four-stage, open-label, multicenter, single-group study of teduglutide in Japanese participants with parenteral-nutrition-dependent short bowel syndrome. Overall enrollment is listed as 11. The arm description specifies 0.05 mg/kg/day by subcutaneous injection over 24 weeks.

The primary Stage 2 outcome was absolute change from baseline in weekly PS volume at Week 24, summarized as a mean and standard deviation. The numerical result and number analyzed are not reported in the registry record. Listed secondary outcomes address teduglutide pharmacokinetics, but their numerical results are not reported in the registry record.

Safety reporting lists serious adverse events affecting 7 of 11 participants, other adverse events affecting 11 of 11, and 1 death. The record lists serious-event terms and percentages but does not provide a comparator group or causal assessment in the information available.