Specified Drug-Use Survey of Trelagliptin Tablets "Survey on Long-term Use in Type 2 Diabetes Mellitus Patients With Severe Renal Impairment or End-stage Renal Disease": Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Specified Drug-Use Survey of Trelagliptin Tablets "Survey on Long-term Use in Type 2 Diabetes Mellitus Patients With Severe Renal Impairment or End-stage Renal Disease" (NCT04285983), a registered phase not stated study. The primary outcome is Number of Participants Who Had One or More Adverse Drug Reactions (ADRs).

2. Clinical Question

The study addresses a safety question in a clinically specific population: people with type 2 diabetes and severe kidney disease receiving trelagliptin during routine care. It does not pose a comparative efficacy question. The description indicates that participants received treatment as part of usual medical care, while the registry supplies no control arm or allocation method. That context matters when interpreting event counts: without a comparison group, the counts describe events observed among treated participants but cannot isolate the contribution of trelagliptin from the underlying illness, other care, or other causes.

3. Trial Design

This was a completed specified drug-use surveillance study of trelagliptin in people with type 2 diabetes mellitus complicated by severe renal impairment or end-stage renal failure. The stated purpose was to evaluate long-term safety in the routine clinical setting. The registry lists the start date as 2020-03-01 and the primary completion date as 2023-01-31. The study status is completed.

The intervention description identifies trelagliptin 25 mg tablets, taken orally once weekly for up to 12 months. Participants received the intervention as part of routine medical care. The record does not describe a randomized assignment or a comparator arm; allocation is not stated. The record therefore does not support treating the study as a controlled comparison or interpreting the observed events as a contrast between treatment strategies.

Enrollment is listed as 89. The primary endpoint’s population is the safety analysis set, defined in the record as all participants who completed the survey; that set included 83 participants in the posted adverse-event information. The registry does not report why the enrollment and safety-set counts differ, participant-level follow-up, or the extent of missing outcome information. Those details should not be inferred from the counts alone.

The study lists four outcome measures, but the registry record does not provide a primary endpoint result in the available information. It also lists no analysis entries. This does not establish what analyses may have been conducted outside the registry; it means the record does not report them. The protocol, detailed analysis plan, sample-size justification, interim analyses, and methods for selecting or adjusting analyses are not reported in the registry record. Consequently, interpretation is limited to the stated design, endpoint definition, and posted safety information.

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: Participants with a historical diagnosis of type 2 diabetes mellitus complicated by severe renal impairment or end-stage renal failure were enrolled. Participants received trelagliptin as part of a routine medical care.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey.

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 Analysis Set, The safety analysis set was defined as all participants who completed the survey.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Had One or More Adverse Drug Reactions (ADRs), measured over Up to Month 12.

The primary endpoint is the number of participants who had one or more adverse drug reactions through Month 12. The record defines an adverse event as an untoward medical occurrence in a participant administered a pharmaceutical product, whether or not it has a causal relationship with that treatment. An adverse drug reaction is an adverse event related to the administered drug. The endpoint therefore concerns reactions judged related to trelagliptin, rather than every medical event occurring during follow-up.

Counting participants with at least one reaction gives a participant-level measure of how many people experienced the outcome. A participant with multiple reactions still contributes to the count of participants with one or more reactions; the count is not the total number of events. This distinction is useful when the clinical question concerns the proportion of treated people affected, while event counts can additionally describe repeated occurrences or different event types.

The endpoint is defined for the safety analysis set, which the record says includes participants who completed the survey. Its timeframe is up to Month 12. However, the numerical primary endpoint result is not reported in the registry record. The separate adverse-event listing includes counts for serious and other adverse events, but those categories are not identified as the primary endpoint count of drug-related reactions. They should not be substituted for it. Without the primary result, its precision, and details of how relatedness was assessed, the endpoint cannot be quantified from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry frames the main outcome as a count of participants with at least one adverse drug reaction. This is a binary participant-level outcome before it is summarized as a count: each participant is classified according to whether the endpoint occurred. A count of affected participants answers how many people met the endpoint definition, but by itself does not describe how many total events occurred, how often events recurred, or how severe each reaction was.

What a participant count can tell us

A participant count can be informative for safety surveillance because it focuses on people affected rather than event episodes. It is important, however, to know the number of participants evaluated and the endpoint definition. The registry identifies the safety analysis set as participants who completed the survey and lists 83 participants in the safety event information. The enrollment count is 89. The registry does not explain the difference between those populations, so the reasons for non-inclusion in the safety set and any effect on interpretation are not reported in the registry record.

The primary endpoint also depends on a judgment about relatedness: an adverse drug reaction is an adverse event related to the administered drug. Such classification is distinct from recording that an event occurred. The record does not describe the process used to assess relatedness, the criteria applied, or whether the assessment was made by investigators, clinicians, or another party. These details can affect which events qualify for the primary endpoint.

Descriptive safety counts and comparison

The serious and other adverse-event entries are descriptive summaries. In general, descriptive counts characterize the participants observed in a study; a comparative treatment effect requires a suitable contrast and an analysis that accounts for the study design. This study has no described comparator, and allocation is not stated. Its event counts cannot establish how many events would have occurred under another treatment or in the absence of trelagliptin.

For binary outcomes, uncertainty may be expressed with a confidence interval around a proportion or a difference between proportions. A confidence interval is a range reflecting sampling uncertainty under a specified statistical method. It helps readers distinguish a more precise estimate from one that remains compatible with a wider range of underlying values. No confidence interval or inferential result for the primary endpoint is reported in the registry record. The posted counts therefore provide no registry-based interval for the primary outcome.

Planning calculations are not observed evidence

The record’s statistical context describes sample-size planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning scenarios: they indicate the number of participants per arm that would be needed under stated assumptions to detect an effect of a chosen fraction of an observed effect. They are not observed power, do not add participants to this surveillance study, and do not turn the study into a controlled comparison. The registry record does not report a protocol sample-size justification, and the actual planning illustration values are not included in the available record.

General power calculations depend on assumptions about the outcome rate, effect to detect, variability, allocation, and analysis method. If those assumptions do not match a future study, its realized precision and ability to detect an effect may differ. For a binary outcome, the required sample size is sensitive to the event frequency and the size of the effect considered important. Because no primary endpoint result or comparison effect is reported, the planning framework cannot be used to infer the study’s ability to identify a treatment difference.

Over-dispersion and outcome structure

Over-dispersion is a general concern when count data vary more than a simple statistical model expects. It can arise when participants differ in their underlying event propensity or when recurrent events cluster within individuals. In such settings, treating every event as independent can understate uncertainty. The primary endpoint in this record is a count of participants with one or more reactions, not a recurrent-event total, and no over-dispersion method is reported in the registry record. It is therefore not possible to say whether recurrent-event models or adjustments were used for other outcomes.

The registry lists four outcome measures but no analysis entries. Detailed model specifications, covariate adjustment, handling of multiple endpoints, and interim analyses are not reported in the registry record. General statistical interpretation should therefore remain tied to the information actually reported: a completed routine-care safety survey, the endpoint definition, the stated analysis population, and descriptive adverse-event counts.

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("Trelagliptin 25 mg")
n      <- c(83)
events <- c(6)
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  Trelagliptin 25 mg  83  6  7.2  2.7  15.1  3.4  14.9  3.4  14.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, but the available record does not identify how analyses across outcomes were prioritized beyond naming the primary endpoint. A multiplicity strategy addresses the increased chance of a false-positive finding when many outcomes or comparisons are tested. Whether such a strategy was specified or used is not reported in the registry record. No analysis entries are listed, and no p-values are reported for the primary endpoint. The record therefore does not permit assessment of multiplicity adjustment or the interpretation of any statistical testing across outcomes.

Missing-data methods are also not reported in the registry record. The safety analysis set is defined as participants who completed the survey, and it contains 83 participants; enrollment is listed as 89. The record does not describe the disposition of participants who were not included in that set, the completeness of follow-up through Month 12, or how incomplete outcome information was handled. It would be inappropriate to assume that every participant had complete observation or that missing outcomes were treated as absent.

As a general matter, restricting an analysis to people who complete follow-up can affect interpretation if completion is related to health, treatment exposure, or event occurrence. This possibility does not show that bias occurred in this study; it identifies why the reasons for completion and missingness matter. The registry does not report sensitivity analyses or methods for addressing possible missing outcome data.

The primary endpoint’s definition is tied to the safety analysis set, but its numerical result is not reported in the registry record. Thus, even apart from multiplicity and missingness, the central endpoint cannot be independently assessed for magnitude or precision from the posted information. Interim analyses and any stopping rules are likewise not reported in the registry record.

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 2.0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nephrogenic anaemia (6.0%), shunt stenosis (4.8%), hyperkalaemia (3.6%), renal impairment (3.6%), fall (3.6%).

The adverse-event listing reports 83 participants at risk, 33 participants with serious adverse events, 10 with other adverse events, and five deaths. These counts describe the safety information posted for the trelagliptin group. They are not comparative estimates, and they do not indicate by themselves whether an event was caused by trelagliptin. The record does not state whether the deaths were considered treatment-related or provide their causes.

The serious-event terms with listed frequencies are nephrogenic anaemia at 6.0%, shunt stenosis at 4.8%, hyperkalaemia at 3.6%, renal impairment at 3.6%, fall at 3.6%, and pneumonia at 2.4%. These are event-term entries, not a complete account of all possible events or a measure of treatment effect. The registry record does not explain the percentage calculation or whether participants could be included under more than one term.

Serious adverse events and adverse drug reactions are not interchangeable categories. Seriousness describes an event classification; drug-reaction status concerns whether the event was considered related to the administered drug. The primary endpoint concerns related reactions, while the posted adverse-event counts are presented as serious and other events. They should be read separately unless the registry explicitly links them.

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

The record documents a completed routine-care surveillance study of trelagliptin in people with type 2 diabetes and severe renal impairment or end-stage renal failure. It describes the intended safety question and provides adverse-event counts for participants receiving trelagliptin 25 mg once weekly for up to 12 months. This contributes descriptive information about events recorded in that setting and population.

The record does not report the numerical result for the primary endpoint, the number of participants with one or more adverse drug reactions. As a result, the primary safety question cannot be answered quantitatively from the available registry information. The serious and other adverse-event counts do not fill that gap, since they are not stated to be counts of drug-related reactions. No confidence interval or other uncertainty estimate for the primary endpoint is reported.

The study also does not include a described comparator or stated allocation method. Without a comparison group, the reported counts cannot show whether event occurrence was higher or lower than under another treatment or no treatment. Nor can the counts establish that trelagliptin caused the events. The underlying condition, other medical care, and other causes may contribute to events; the record does not separate these influences.

The serious-event terms and death count are not evidence on their own of a causal relationship, and the listed percentages do not provide a comparative risk estimate. Conversely, an absence of a reported primary endpoint result does not mean that no reactions occurred. It means the registry record does not supply the endpoint value needed to describe their frequency.

The findings should therefore be understood as a limited descriptive record of safety observations, not a definitive estimate of treatment-attributable risk, a test of efficacy, or a comparison of treatment options. The registry does not report the detailed analysis plan, missing-data handling, relatedness assessment process, or precision estimates that would support stronger statistical conclusions.

14. Why This Trial Matters Statistically

This study is statistically relevant because it concerns safety surveillance in a defined population with type 2 diabetes and severe renal impairment or end-stage renal failure. The routine-care setting distinguishes it from a randomized comparison: participants received trelagliptin as part of medical care, and the record does not describe a control arm or allocation method. That setting can capture events observed during clinical use, while also limiting causal interpretation.

The endpoint definition highlights an important distinction in safety analysis. An adverse event is a medical occurrence after drug administration and need not be caused by the drug; an adverse drug reaction is an event considered related to the drug. A participant count for reactions is therefore not interchangeable with an all-event count, and relatedness judgments matter to the endpoint. The primary numerical result is not reported in the registry record, making the distinction especially important when reading the separate serious and other event counts.

Completer-defined safety populations also deserve attention. The registry lists enrollment of 89 and a safety analysis set of 83 participants who completed the survey. Since the record does not describe the difference or how incomplete follow-up was handled, readers cannot determine whether the observed set fully represents everyone enrolled. This is a general concern about analysis populations, not evidence that the study’s results are biased.

Finally, counts without a comparator or uncertainty estimates are descriptive rather than comparative. They can indicate what the registry records in this group, but they cannot establish how the event burden differs from another treatment. The study’s value is therefore tied to transparent limits: the population, care context, outcome definition, and reported event counts are clear, while the primary endpoint result and analytic details are not reported in the registry record.

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 in the registry record is that the numerical result for the stated primary endpoint is not reported. The endpoint asks for the number of participants with one or more adverse drug reactions, but the available safety counts are presented as serious and other adverse events. They cannot be assumed to represent the primary endpoint.

The study has no described comparator, and allocation is not stated. Accordingly, it cannot estimate a comparative treatment effect or distinguish events attributable to trelagliptin from events associated with the underlying illness, other care, or other causes. The record also does not report how drug relatedness was assessed, how serious-event status was determined, or the causes and treatment-relatedness of the five deaths.

The difference between enrollment of 89 and the safety analysis set of 83 is not explained. The record defines the safety set by survey completion but does not describe participant disposition, completeness of follow-up, or handling of missing outcomes. Those omissions limit assessment of the analysis population and potential missing-data concerns.

Although four outcome measures are listed, the registry record does not report analysis entries, confidence intervals, p-values, detailed statistical methods, multiplicity handling, interim analyses, or a protocol-based sample-size justification. The record does not explain the calculation of the listed event-term percentages or whether people could contribute to more than one term. These limitations do not establish that unreported procedures were absent; they mean they are not reported in the registry record. Interpretation should remain descriptive and should not extend beyond the information documented.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Specified Drug-Use Survey of Trelagliptin Tablets "Survey on Long-term Use in Type 2 Diabetes Mellitus Patients With Severe Renal Impairment or End-stage Renal Disease" — NCT04285983.
• Registry record last updated 2024-08-23; status last verified 2024-03.
• Results first posted 2024-08-23.
• 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 completed study evaluated the long-term safety of trelagliptin in routine clinical care among people with type 2 diabetes complicated by severe renal impairment or end-stage renal failure. Participants received trelagliptin 25 mg orally once weekly for up to 12 months. Enrollment is listed as 89, and the safety analysis set is defined as participants who completed the survey, with 83 participants listed in the adverse-event information.

The primary endpoint was the number of participants with one or more adverse drug reactions through Month 12. Its numerical result is not reported in the registry record. The adverse-event listing reports 33 participants with serious adverse events, 10 with other adverse events, and five deaths; it also lists several serious-event terms with percentages. These counts are descriptive and do not establish drug causation.

No comparator or allocation method is described. The registry record does not report the primary endpoint’s uncertainty, detailed analysis methods, missing-data handling, or multiplicity approach. The available information supports a limited description of the surveillance study and its posted safety entries, not a comparative or causal conclusion.