Open-Label Safety and Efficacy of the Sufentanil Sublingual Tablet 30 mcg for Acute Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label Safety and Efficacy of the Sufentanil Sublingual Tablet 30 mcg for Acute Pain (NCT02447848), a na phase 3 study. The primary outcome is Time-weighted Summed Pain Intensity Difference (SPID) Over the 1-hour (SPID1)..

2. Clinical Question

3. Trial Design

The registry identifies this as a Phase 3, multicenter, open-label trial of the sufentanil sublingual tablet 30 mcg for moderate-to-severe acute pain in an emergency room setting. The study is listed as completed. Its start is recorded as 2015-10, and its primary completion as 2016-06. Talphera, Inc is listed as the sponsor.

The design is single-group, with allocation listed as not applicable and masking listed as none. The record describes one intervention: sufentanil sublingual 30 mcg tablet. Patients may be administered one tablet every 60 minutes as needed during the study period. A control group, random assignment, or blinded assessment is not described. Consequently, the record supports a description of outcomes and safety observations in the treated group, but not a direct treatment-versus-control estimate.

The registry lists enrollment as 76. That figure is the recorded enrollment, not a reported count of patients with usable primary endpoint data. The number contributing to the endpoint, the number receiving a dose, and the analysis population are not reported in the registry record. The study period's duration and further details of the dosing process are also not reported.

The primary efficacy endpoint was time-weighted SPID1, derived from patient questionnaire data and assessed over one hour. The listed secondary outcomes are time-weighted TOTPAR1 and pain intensity at each evaluation time point. The record lists three outcome measures but no analysis results. The registry record does not describe the statistical analysis plan, a sample-size justification, or interim analyses.

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

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Time-weighted Summed Pain Intensity Difference (SPID) Over the 1-hour (SPID1)., measured over One hour.

SPID1 is intended to summarize the change in reported pain intensity during the one-hour period after the first dose. Pain intensity is rated using an 11-point numerical rating scale, where 0 means no pain and 10 means worst possible pain. At each assessment after dosing, pain intensity difference is defined as baseline pain intensity minus the rating at that assessment. A positive difference therefore represents a lower pain rating than at baseline, while a negative difference represents a higher rating.

The endpoint is time-weighted: it combines the pain-intensity differences over the one-hour study period while accounting for when the ratings were taken. The stated assessment schedule includes baseline and measurements at 0.25 (15 min), 0.5 (30 min), 0.75 (45 min), 1, 2, 3, 4, and 5 hours following the first dose. SPID1 concerns the one-hour period, not the later scheduled assessments.

Summarizing repeated pain ratings in a single endpoint can describe the direction and accumulated magnitude of change over the specified period. The registry identifies the mean as the summary parameter and the standard error as the dispersion measure. However, the mean and standard error for SPID1 are not reported in the registry record. The record states that observed SPID scores ranged from -.70 to 8.00, but that range alone does not identify the group mean, its precision, or how individual scores were distributed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary measure represent?

SPID1 is a continuous endpoint constructed from repeated pain-intensity ratings. The registry describes an 11-point numerical rating scale, from 0 for no pain to 10 for worst possible pain. Pain intensity difference at each assessment is baseline pain intensity minus pain intensity at that assessment. This sign convention matters: a positive difference means the rating is lower than baseline, while a negative difference means it is higher. The endpoint then combines these differences over the one-hour period using time weighting.

Time weighting is a way to represent a sequence of measurements across an interval rather than treating each recorded value as if it described the entire interval equally. In general, a time-weighted summary reflects both the magnitude of changes and the periods over which they apply. The registry identifies SPID1 as the primary efficacy measure and gives a measurement schedule, but does not report further computational details beyond its definition as time-weighted summed pain intensity difference over one hour.

Why report a mean and standard error?

The registry lists the mean as the summary parameter and standard error as the dispersion measure for the continuous endpoint. A mean describes the central value of a group of measurements. A standard error describes the precision of an estimated mean: in general, smaller standard errors indicate less sampling uncertainty around that estimate, while larger standard errors indicate more. A standard error is not a description of how much individual patients' measurements vary. That individual-level spread is a different statistical quantity.

Neither the primary mean nor its standard error is reported in the registry record. There is consequently no reported estimate from which to assess the average score or its precision. A confidence interval would express a range of values compatible with an estimate under a statistical procedure, but no confidence interval for SPID1 is reported. The observed score range, -.70 to 8.00, supplies neither the mean nor a measure of its uncertainty.

What can a single-group design estimate?

A single-group study can describe outcomes observed among participants in that group. It does not, by itself, provide a concurrent estimate of what would have happened to comparable participants under a different treatment or control condition. Open-label status means that masking is listed as none. General methodological considerations include possible influence of expectations on reported outcomes and the difficulty of separating treatment-associated change from change over time or other care. The registry does not report that these influences occurred in this trial; they are limits on the interpretation of an uncontrolled design.

Allocation is listed as not applicable, and the study model is single group. The record therefore does not describe randomization or an assigned comparator. Any comparison with another population or study would require information not reported in the registry record, as well as attention to differences in patient selection, setting, measurement, and follow-up. No such comparative analysis is reported.

How should repeated measurements be understood?

The primary endpoint uses pain ratings at baseline and at scheduled times following the first dose. Repeated measurements can describe the pattern of a clinical measure over time, while a summary such as SPID1 compresses part of that pattern into one value. Compression makes an endpoint easier to summarize but can conceal the specific trajectory: two sets of ratings can have different patterns even if their summaries are similar. The registry separately lists pain intensity at each evaluation time point as a secondary outcome, but reports no estimates for those measurements.

The time-weighted SPID1 period is one hour. Additional assessments are listed at later times, including 2, 3, 4, and 5 hours, but these later observations are not part of the stated one-hour primary endpoint. The registry also lists time-weighted TOTPAR1 as a secondary outcome. Its detailed definition and results are not reported in the registry record, so its precise construction should not be inferred from its name alone.

What do planning illustrations mean?

Any sample-size figures associated with planning are illustrations based on a stated fraction of the observed effect, not the design or enrollment target used for this trial. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe a hypothetical two-arm planning exercise, whereas this trial is recorded as single-group. Such figures are not observed power and should not be read as evidence that the trial was planned, randomized, or analyzed with two arms.

In general, a planning calculation estimates the number of participants that a proposed design might require under chosen assumptions. It is conditional on the effect size, variability, allocation, and analysis assumptions used. It does not establish the precision or power actually achieved in a completed study. The registry record does not report a trial-specific sample-size justification, and no sample-size assumptions should be attributed to the original study beyond what the record states.

More broadly, the registry does not report inferential tests, confidence intervals, or a detailed statistical analysis plan for the primary endpoint. The meaning of a test or interval depends on the analysis population, handling of missing observations, model, and prespecified decision rules. Those details are not reported in the registry record, so they cannot be reconstructed from the endpoint description alone.

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("Sufentanil Sublingual Tablet 30 mcg")
n   <- c(76)
m   <- c(2.11)
sp  <- c(0.24)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Sufentanil Sublingual Tablet 30 mcg  76  2.110  2.092  1.632  2.588

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures. The primary measure is time-weighted SPID1; the listed secondary outcomes are time-weighted TOTPAR1 and pain intensity at each evaluation time point. The record does not report analysis results for these measures, and it does not explain whether or how the statistical interpretation of multiple outcomes was addressed. In general, when several outcomes or repeated tests are considered, the chance of a seemingly notable result can depend on how many analyses are performed and how they are selected. No multiplicity procedure or hierarchy is reported in the registry record.

The registry does not describe how missing pain ratings were handled, whether all scheduled assessments were available, or how participants with incomplete data were included in an analysis. It does not report the number contributing data to the primary endpoint or define an analysis population. Enrollment is listed as 76, but that does not establish how many had evaluable endpoint data or whether all enrolled participants were included in any efficacy summary.

The record also does not report an analysis plan, rules for handling protocol deviations, or details of any interim analysis. Those elements should not be inferred from the Phase 3 designation or from the fact that the study is listed as completed. Without the endpoint estimates and these analysis details, readers cannot assess the consequences of missing data, confirm which population was analyzed, or determine how results across outcomes were interpreted.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina pectoris (1.3%).

The registry lists one serious adverse event among 76 at risk in the sufentanil sublingual tablet 30 mcg group. It lists 12 other adverse events among 76 at risk. Angina Pectoris is the reported serious adverse event term, with 1.3% listed. These are descriptions of the group in this trial, not comparisons against another treatment.

The serious and other adverse event counts are presented as separate categories in the record. They should not be added together to create a participant total, since the registry does not state whether categories overlap. The at-risk count is a registry figure; details about exposure duration, event collection, and follow-up are not reported in the registry record. The record also does not report deaths. That absence should be read as information not reported in the registry record, rather than evidence that no deaths occurred.

Event counts in a single-group study can identify what was reported in that group, but do not show whether the event frequency differs from what would occur with another treatment or without the intervention. The registry safety figures therefore support a descriptive account only and should not be interpreted as a comparative safety estimate.

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

The registry record documents a Phase 3, open-label, single-group study of a sufentanil sublingual tablet 30 mcg in an emergency room setting for moderate-to-severe acute pain. It defines a primary pain endpoint based on time-weighted changes from baseline over one hour and provides a range of observed SPID scores, from -.70 to 8.00. The stated score direction makes positive values consistent with a decrease in pain intensity relative to baseline and negative values consistent with an increase.

That information does not supply the average SPID1 result or its precision. The primary endpoint mean and standard error are not reported in the registry record, and no analysis results are listed. The score range cannot establish the average change, show how scores were distributed, or provide a confidence interval. It therefore does not support a quantified estimate of the primary endpoint's group-level result.

The single-group design also limits causal interpretation. Without a comparator, observed changes cannot be contrasted with outcomes under another condition within the same study. Open-label status and the lack of a control group are relevant design features, but do not establish that any specific source of bias affected the observations.

The adverse event figures describe events listed for the trial group. They do not quantify a difference in safety relative to a comparator. Missing information about the analysis population, missing data, follow-up, and statistical plan further limits what can be inferred. The registry record is informative about the question studied and the way SPID1 was defined, but it does not report enough efficacy analysis to characterize the primary endpoint result or its uncertainty.

14. Why This Trial Matters Statistically

This trial is statistically notable for the contrast between a clearly described continuous endpoint and the absence of a reported analysis result for that endpoint. SPID1 is defined through repeated pain ratings, baseline subtraction, and time weighting over one hour. That detail helps explain what the intended measure represents. Yet without the mean and standard error, readers cannot assess the magnitude or precision of the group-level result.

The single-group, open-label design also makes the distinction between observing change and estimating a comparative treatment effect especially important. A baseline-referenced measure can summarize how ratings differ from baseline, but it does not provide the counterfactual comparison needed to determine how those ratings would have changed under another condition. This is a general design principle, not a claim about the cause of any observed scores in this trial.

The record lists both efficacy outcomes and safety counts, but the two kinds of information have different interpretive limits. The observed SPID range does not replace a mean or uncertainty estimate. Likewise, adverse event counts in one group do not establish a comparative safety difference. The case illustrates why outcome definitions, analysis results, and study design all matter when interpreting clinical trial records.

Planning illustrations, if consulted, also need to be kept separate from the actual design and findings. The registry's stated illustration assumptions describe a hypothetical two-arm planning calculation; the actual trial is listed as single-group. Such planning quantities are not observed power and cannot fill the gap left by unreported endpoint analyses.

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 for statistical interpretation is that the registry record does not report the primary endpoint mean or standard error, despite describing SPID1 as the primary efficacy endpoint. It gives a range of observed SPID scores, but that range cannot characterize the average result or its precision. The record lists zero analyses, so no reported efficacy estimate or inferential result is available for interpretation.

The single-group, open-label design has no control arm described. It can support descriptive observations in the study group, but cannot establish a randomized comparison. Because the registry lists no masking, subjective pain ratings may also be susceptible in general to expectation or reporting influences; the record does not establish whether such influences occurred.

Additional details needed to assess the endpoint analysis are not reported in the registry record. These include the number of participants contributing primary endpoint data, the analysis population, the handling of missing ratings, and further statistical methods. The registry lists later pain assessments and secondary outcomes, but does not report their analysis results or how multiple outcomes were treated.

The dosing description says one tablet may be administered every 60 minutes as needed during the study period, but the duration of that period and the actual dosing received are not reported. The record does not provide further details about follow-up for adverse events. The safety counts are therefore descriptive and cannot be used to compare event risks with a control group. Deaths are not reported in the registry record, which does not establish whether any occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-Label Safety and Efficacy of the Sufentanil Sublingual Tablet 30 mcg for Acute Pain — NCT02447848.
• Registry record last updated 2017-10-19; status last verified 2017-07.
• Results first posted 2017-10-19.
• 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

NCT02447848 is a completed Phase 3, multicenter, open-label, single-group trial of sufentanil sublingual tablet 30 mcg for moderate-to-severe acute pain in an emergency room setting. The registry lists enrollment as 76 and identifies Talphera, Inc as the sponsor.

The primary endpoint is time-weighted SPID1 over one hour, based on pain intensity ratings from an 11-point numerical rating scale. The registry states that observed SPID scores ranged from -.70 to 8.00, but does not report the endpoint mean, standard error, or analysis results. Secondary outcomes listed are time-weighted TOTPAR1 and pain intensity at each evaluation time point.

The record lists one serious adverse event and 12 other adverse events, each among 76 at risk; Angina Pectoris is listed as a serious adverse event term at 1.3%. A comparator, analysis population, missing-data approach, and statistical analysis plan are not reported in the registry record.