A Open-label Study to Evaluate the Safety of TRV130 in Patients With Acute Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Open-label Study to Evaluate the Safety of TRV130 in Patients With Acute Pain (NCT02656875), a na phase 3 study. The primary outcome is Number of Patients That Experienced a Treatment-emergent Adverse Event.

2. Clinical Question

3. Trial Design

This was a Phase 3, open-label, single-group study of TRV130 in patients with acute pain. The registry record identifies Trevena Inc. as the sponsor and reports the study as completed. The recorded start was 2015-12, and primary completion was 2017-05. Enrollment was 768 participants.

There was no masking and no randomized allocation. Participants received TRV130 by IV bolus, PCA administration, or both, with the approach determined by the investigator. The brief description says patients could receive treatment for a duration not to exceed 14 days. For clinician-administered bolus dosing, it describes an initial dose, possible supplemental dosing when clinically indicated, and subsequent dosing every 1 to 3 hours as needed. For PCA, it identifies a loading dose, demand dose, and lockout, but the available description does not give the complete regimen.

The design is suited to describing safety events observed among participants exposed to the study drug under the study’s treatment conditions. Because it has a single group and no control arm, the design cannot isolate the contribution of TRV130 from other influences on adverse events. For example, the study population had acute pain associated with medical conditions or surgery, and participants’ circumstances and clinical care may also be relevant to observed events. The registry record does not report a protocol rationale for the design, detailed eligibility criteria, or the planned statistical analysis.

Enrollment is not automatically the same as the number included in each outcome analysis. The registry record does not report a separate analysis-population definition or explain whether every enrolled participant contributed to each safety summary. The posted figures should therefore be read as registry-reported participant counts, not as evidence that all enrolled participants were necessarily assessed in an identical way.

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

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 Patients That Experienced a Treatment-emergent Adverse Event, measured over From first dose through 3 days after last dose, approximately 4 days.

The primary endpoint is the number of participants who experienced a treatment-emergent adverse event. The observation window begins with the first dose and continues through 3 days after the last dose, approximately 4 days. A participant count expresses how many people had an event during the defined period; it is a safety measure, not a direct measure of pain relief or comparative benefit.

Counting participants with events is useful in safety studies because it focuses on whether an event affected a person, rather than simply counting repeated occurrences in the same person as separate participants. In general, participant counts can make the frequency of affected people easier to interpret. They do not, by themselves, describe the event’s severity, duration, relationship to treatment, or clinical consequences. Those details require separately reported information.

The registry record identifies this endpoint but does not separately report a primary-endpoint result or analysis. The posted adverse-event summaries report 26 participants in the serious adverse-event category and 403 in the other adverse-event category. These categories are not a substitute for a fully described primary-endpoint analysis: the record does not explain their relationship to the primary endpoint, provide event-level detail for the primary outcome, or report an inferential comparison. No efficacy endpoint is described in the registry information for this trial.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s statistical structure is a single-group safety assessment. In a single-group study, outcomes are described among participants receiving the study intervention. Without a concurrent comparison group, a treatment contrast cannot be estimated from the study design. The listed safety counts can be read as descriptive summaries, but they do not establish what would have happened to the same kinds of participants under a different treatment.

What does a participant count measure?

A count of participants with an event records the number of distinct people who experienced that event or event category. It is different from an event count, which may count repeated occurrences in one person multiple times. The primary endpoint is worded as the number of patients who experienced a treatment-emergent adverse event, and the unit is participants. However, the registry record does not separately provide the primary-endpoint result or define how event records were grouped for that outcome. The safety summaries list 26 participants for serious adverse events and 403 for other adverse events. Those entries should be interpreted according to their category labels rather than silently combined into a different endpoint.

Why does the observation window matter?

An adverse-event measure depends on when participants are observed. The primary endpoint timeframe begins at first dose and continues through 3 days after last dose, approximately 4 days. This gives the reader a stated window for interpreting the endpoint, but it does not describe every detail of follow-up, such as whether observation was complete for every participant or how events with uncertain onset were handled. Those details are not reported in the registry record. In general, different observation periods can yield different opportunities to detect events, so event counts should be read together with their stated timeframe.

What is a confidence interval?

In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the statistical method used. A narrow interval indicates greater statistical precision than a wide interval, while an interval around a single-group event count would not create a comparison with another treatment. No confidence interval for the primary endpoint is reported in the registry record. Without one, the statistical precision of that endpoint cannot be assessed from the posted information. A count is still a useful descriptive result, but it does not show how much uncertainty surrounds an underlying event frequency.

What do significance tests and power mean?

In general, a significance test evaluates data against a specified statistical hypothesis, and power is a design-stage concept describing the chance that a planned test will detect a specified effect if that effect is present. Neither concept turns a single-group count into evidence of a controlled treatment difference. The registry record lists no analyses, test results, p-values, or trial-specific power calculation. A significance level of 0.05, equal allocation between two arms, and a normal approximation are stated for planning illustrations based on fractions of an observed effect. Those illustrations are not the trial’s own design or observed power. They cannot be interpreted as a randomized comparison conducted in this single-group study, and no numerical planning result is reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion occurs when the variation in data is greater than a statistical model expects. It can make standard errors too small if a model assumes less variation than the data contain, leading to overly precise inference. This concept is relevant to some count-data analyses, especially when events cluster within participants or vary more than a simple model anticipates. The registry record does not describe a count model, an over-dispersion assessment, or any model-based primary analysis. The listed outcomes are participant counts, and no claim about an over-dispersion adjustment can be made for this study.

What can the posted analysis establish?

The registry record reports the study design, endpoint definition, and safety summaries, but it does not report an analysis plan or an inferential outcome analysis. The distinction matters: descriptive results summarize the observed study group, whereas inferential comparisons depend on a specified design and method. No analysis result in the record supports a treatment-versus-control estimate. The available statistics are therefore best read as a registry description of observed safety events, with the limits of a single-group, open-label study.

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("TRV130")
n      <- c(768)
events <- c(490)
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  TRV130  768  490  63.8  60.3  67.2  60.3  67.1  60.3  67.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one outcome measure and lists no analyses. It does not report a multiplicity strategy, such as an approach to controlling the chance of false-positive findings across multiple statistical tests. Because no set of inferential tests or p-values is listed, there is no reported multiplicity adjustment to interpret. The absence of a reported adjustment does not establish that none was planned in study documents; the statistical plan is not reported in the registry record.

Missing-data handling is also not reported in the registry record. The available information does not describe how participants with incomplete follow-up were handled, whether any event status was unknown, or how missing observations affected the safety summaries. No imputation method or sensitivity analysis is described. This matters because safety summaries depend on the amount and completeness of observation, but the record does not permit an assessment of those features.

The record lists 768 participants enrolled and 768 at risk for the TRV130 safety categories. It does not provide a separate analysis-population definition, a participant flow, or a statement that enrollment and every endpoint-specific population were identical. The listed at-risk denominators are useful context for the posted counts, but they do not explain exclusions or missing assessments. No intention-to-treat, per-protocol, or other named analysis population is reported in the registry record.

These omissions limit assessment of how robust the summaries are to incomplete information and how the primary endpoint was analyzed. They do not change the descriptive nature of the reported safety counts, and they do not justify assuming a particular missing-data or multiplicity procedure.

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: nausea (0.3%), postprocedural hematoma (0.3%), atrial fibrillation (0.1%), flatulence (0.1%), intra-abdominal hemorrhage (0.1%).

The serious adverse-event summary lists 26 participants with serious adverse events among 768 at risk in the TRV130 group. The registry also lists 0 deaths. These are participant counts; the record does not provide a comparison group or an adjusted estimate of risk. The serious-event terms and percentages listed include Nausea at 0.3%, Postprocedural Hematoma at 0.3%, Atrial Fibrillation at 0.1%, Flatulence at 0.1%, Intra-Abdominal Hemorrhage at 0.1%, and Small Intestinal Obstruction at 0.1%.

In general, a serious adverse event is a safety classification, not a statement that the event was caused by treatment. The registry record does not provide event narratives, individual-level timing, treatment attribution, or a complete account of outcomes for each event. The listed term-specific percentages should be read as reported, not combined into a total; participants may have experienced more than one term, and the record does not describe overlap.

The count of 0 deaths describes the recorded study group and does not mean that a risk is impossible or absent in other settings. With no control group, these results cannot show whether the frequency of serious events was higher or lower than it would have been under another treatment. They are descriptive safety information, not a comparative safety conclusion.

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

The results mean that the registry record describes safety events observed among participants treated with TRV130 in an open-label, single-group study. It lists 768 participants at risk, 26 with serious adverse events, 403 in the other adverse-event category, and 0 deaths. The primary endpoint is defined as the number of participants experiencing a treatment-emergent adverse event during the stated timeframe, but its result is not separately reported as a primary-outcome analysis.

These results do not establish that TRV130 caused the reported events. Adverse events can occur during treatment for reasons that the study design cannot separate from treatment effects. Without a randomized comparator, there is no controlled estimate of how the event counts compare with another treatment or with no exposure. The study is open-label, so it also does not provide a masked comparison.

The data do not establish the frequency of events in all patients with acute pain, or in patients whose characteristics differ from those enrolled. The registry information does not provide detailed participant characteristics, a separate analysis population, or a full account of follow-up completeness. Generalizing beyond the study group therefore requires information not reported in the registry record.

The posted serious-event terms and percentages offer some detail about the kinds of serious events recorded, but they do not describe severity beyond the category, duration, outcome, or treatment attribution for each event. They also should not be combined into a single rate because the record does not show whether participants or events overlap across terms. The recorded 0 deaths is a count in this study, not proof that mortality risk is absent.

In general, safety findings are more informative when the event definitions, observation periods, analysis populations, and uncertainty estimates are all clear. The record provides a primary endpoint timeframe and group at-risk counts, but does not report a confidence interval or a separate inferential analysis for that endpoint. The appropriate interpretation is therefore limited to the reported descriptive information; it is not a conclusion about comparative safety or treatment efficacy.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of what a single-group safety study can and cannot show. The registry record describes an open-label study with 768 participants enrolled and reports participant counts for serious and other adverse events. Those summaries can document events observed under the study’s treatment conditions and identify the stated timeframe for the primary safety endpoint.

The design also makes the limits of descriptive safety evidence clear. A single group has no concurrent control against which to estimate a treatment difference. This prevents a causal comparison, even when event counts are recorded precisely. The open-label design and the lack of reported inferential analyses further mean that the posted figures should not be presented as a statistical test of comparative safety.

The record distinguishes the endpoint’s intended measure from the results actually reported. It names a participant-count outcome for treatment-emergent adverse events but does not separately provide a primary-endpoint analysis. That distinction is useful when reading trial registries: an outcome definition is not itself an outcome result, and a result count is not necessarily a full analysis with a stated population and uncertainty estimate.

The registry also illustrates why safety summaries require careful attention to categories and denominators. The serious adverse-event participant count, the other adverse-event count, and the term-specific percentages describe different aspects of the record. They should not be combined or treated as interchangeable. Taken together, the information offers a descriptive account of recorded events while leaving comparative inference, precision, and some analysis details unresolved.

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 trial-specific limitation is the single-group, open-label design. There is no randomized control group, so the reported safety counts cannot estimate a comparative treatment effect or separate treatment-related events from events associated with participants’ conditions, surgery, or other circumstances. The registry record does not report a masking procedure because masking is listed as none.

The primary endpoint is defined, including its observation period, but a separate primary-endpoint result and analysis are not reported in the registry record. The record also lists no analyses. Consequently, no inferential estimate, p-value, or confidence interval is available to characterize statistical precision. The posted safety counts remain descriptive.

The record does not report detailed baseline characteristics, participant flow, analysis-population definitions, missing-data handling, or completeness of follow-up. Although it gives 768 enrolled and 768 at risk for the safety categories, it does not explain whether all enrolled participants contributed to every outcome assessment or how incomplete records were handled. The detailed statistical plan and any trial-specific sample-size justification are not reported in the registry record.

The serious adverse-event list gives selected terms and percentages but no event narratives, timing, individual outcomes, or treatment attribution. The record does not say whether participants experienced multiple terms, so term-specific percentages cannot be added to form a total. The 0 deaths entry is limited to the recorded study group and does not establish a general risk estimate.

Finally, the described treatment could involve bolus dosing, PCA, or both, as determined by the investigator. The registry record does not give the complete PCA regimen in the available description. These features limit detailed interpretation of exposure patterns and reinforce that the results describe this study rather than a controlled comparison across treatment strategies.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Open-label Study to Evaluate the Safety of TRV130 in Patients With Acute Pain — NCT02656875.
• Registry record last updated 2020-09-24; status last verified 2020-09.
• Results first posted 2020-09-24.
• 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 NCT02656875, a completed Phase 3, open-label, single-group study of TRV130 in patients with acute pain for which parenteral opioid therapy was warranted. It lists 768 participants enrolled, a study start of 2015-12, and primary completion in 2017-05. TRV130 was administered by IV bolus, PCA, or both, as determined by the investigator, for a duration not to exceed 14 days.

The primary endpoint was the number of participants experiencing a treatment-emergent adverse event from first dose through 3 days after last dose, approximately 4 days. The safety summaries list 26 participants with serious adverse events, 403 in the other adverse-event category, and 0 deaths. The registry record does not report a separate primary-endpoint analysis, a comparator, or inferential results. These figures are descriptive and do not establish comparative safety or event causation.