This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Long-term Open-Label Safety Study to Evaluate EN3409 (NCT01755546), a na phase 3 study. The primary outcome is Change From Baseline to Week 48 in Daily Average NRS Pain Intensity Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01755546 |
| Phase | Phase 3 |
| Condition | Low Back Pain, Osteoarthritis, Neuropathic Pain |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 304 |
| Arms in the primary outcome | n/a |
| Lead sponsor | BioDelivery Sciences International |
| Results posted | Yes |
2. Clinical Question
Population
People with moderate to severe chronic pain requiring continuous around-the-clock opioid analgesia for an extended period. The listed conditions are low back pain, osteoarthritis, and neuropathic pain. The primary endpoint population is named the Efficacy Population, but its eligibility details are not reported in the registry record.
Intervention
EN3409, described as buprenorphine HCI buccal film at doses ranging from 300-900 mcg twice daily.
Comparator
There is no separate comparator group. The study is listed as single group, with allocation recorded as not applicable and masking as none.
Primary question
What was the change from baseline to week 48 in daily average NRS Pain Intensity Score among the Efficacy Population? The registry record names this endpoint but does not report its numerical result.
The primary question concerns change in pain score during an open-label study, not a randomized comparison of EN3409 with another treatment or with a control condition. That distinction matters: a before-and-after change can describe the observed course of scores among participants included in the analysis, but it cannot by itself isolate the contribution of the intervention from other influences over time.
The registry lists 304 participants as the enrollment and identifies low back pain, osteoarthritis, and neuropathic pain as conditions. It does not report how participants were distributed across those conditions, how many contributed to the primary endpoint, or how the Efficacy Population was defined. The study's stated purpose also includes safety and tolerability, while the primary endpoint is a pain-intensity measure.
3. Trial Design
This is a phase 3, open-label, long-term, single-group study of EN3409. The registry lists no masking and records allocation as not applicable. Accordingly, the design does not contain a randomized control arm for a like-for-like treatment comparison. The sponsor is BioDelivery Sciences International. Enrollment is 304; the listed start is 2012-12, primary completion is 2014-10, and status is completed.
The intervention is described as buprenorphine HCI buccal film at doses ranging from 300-900 mcg twice daily. The registry does not report how dose selection or adjustment occurred, how long each participant was followed, or how treatment exposure varied. The official title describes a study of safety, tolerability, and analgesic efficacy in people with moderate to severe chronic pain requiring continuous around-the-clock opioid analgesia for an extended period.
The primary endpoint is a continuous measure: change from baseline to week 48 in daily average NRS Pain Intensity Score. The registry identifies the Efficacy Population for this outcome and specifies the mean and standard deviation as the intended summary measures. It does not report the endpoint's observed mean change or standard deviation.
Because the study has one group and no masking, findings describe outcomes recorded within that study setting. They do not constitute a randomized comparison. The registry record does not report a protocol-level account of the analysis methods, dose management, follow-up schedule beyond the endpoint timeframe, or reasons participants may not have contributed endpoint or safety data.
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.
Screened and Taper (Rollover and DeNovo)
| Stage | Overall |
|---|---|
| STARTED | 304 |
| COMPLETED | 294 |
| NOT COMPLETED | 10 |
Reasons for not completing this period:
| Reason | Overall |
|---|---|
| Protocol Violation | 1 |
| Withdrawal by Subject | 3 |
| Lost to Follow-up | 1 |
| Any other reason and screen failures | 5 |
Titration Phase
| Stage | Overall |
|---|---|
| STARTED | 294 |
| COMPLETED | 224 |
| NOT COMPLETED | 70 |
Reasons for not completing this period:
| Reason | Overall |
|---|---|
| Adverse Event | 11 |
| Lack of Efficacy | 18 |
| Protocol Violation | 9 |
| Lost to Follow-up | 2 |
| Other and Continuing | 22 |
| Withdrawal by Subject | 8 |
Long Term Treatment
| Stage | Overall |
|---|---|
| STARTED | 224 |
| COMPLETED | 103 |
| NOT COMPLETED | 121 |
Reasons for not completing this period:
| Reason | Overall |
|---|---|
| Adverse Event | 12 |
| Lack of Efficacy | 6 |
| Protocol Violation | 10 |
| Withdrawal by Subject | 35 |
| Lost to Follow-up | 17 |
| other and ongoing | 41 |
Analysis population for the primary outcome, as defined in the registry: Efficacy Population
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Baseline at start of Long-Term Treatment Phase
| Characteristic | Unit | Overall |
|---|---|---|
| Participants analysed | 224 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 193 |
| Age, Categorical: >=65 years | Participants | 31 |
| Age, Continuous | Years | 52 (SD 11.80) |
| Sex: Female, Male: Female | Participants | 125 |
| Sex: Female, Male: Male | Participants | 99 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 39 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 185 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 3 |
| Race (NIH/OMB): Asian | Participants | 6 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 57 |
| Race (NIH/OMB): White | Participants | 158 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Weight (kg) | kilograms | 92.2 (SD 21.57) |
| Height (cm) | centimeters | 169.5 (SD 10.39) |
| BMI (kg/m^2) | kg/m^2 | 32.1 (SD 7.20) |
| NRS Pain Intensity | units on a scale | 3 (SD 1.30) |
| Chronic Pain: Lower Back Pain | Participants | 222 |
| Chronic Pain: Neuropathic Pain | Participants | 1 |
| Chronic Pain: Osteoarthritis | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline to Week 48 in Daily Average NRS Pain Intensity Score, measured over 48 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline to week 48 in daily average NRS Pain Intensity Score, expressed in units on a scale. The registry describes the NRS as a segmented version of a visual analog scale used to measure pain. Its scale runs from 0, meaning no pain, to 10. Scores greater than 0 and up to 3 are categorized as mild, scores greater than 3 and up to 6 as moderate, and scores greater than 6 and up to 10 as severe.
Daily averaging gives a summary of reported pain intensity across a day rather than relying on one score alone. In general, a change endpoint expresses how a measure at follow-up differs from its baseline value. The mean summarizes the average change among participants included in the analysis, while the standard deviation describes how spread out individual changes are around that mean. These are distinct features: an average alone does not show how similar or varied participants' changes were.
The registry record identifies week 48 as the endpoint timeframe and the Efficacy Population as the population for the measure. It does not report the mean change, its standard deviation, the number analyzed, or a confidence interval. Without the numerical estimate and its uncertainty, the direction and size of the recorded change cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary endpoint and its planned summary as a mean change with a standard deviation, but it does not report a numerical endpoint result. It also lists 0 analyses. As a result, there is no posted estimate of mean change from baseline to week 48, no standard deviation for that change, and no reported confidence interval or p-value to interpret. The endpoint definition alone is not evidence of the direction or magnitude of participants' scores.
In general, the mean change describes the average change among participants included in an analysis. A standard deviation gives information about variation between their changes, not the precision of the estimated mean. A confidence interval, if reported, would convey the range of values compatible with the data and the analysis assumptions. None is reported for this endpoint in the registry record, so the precision of any mean change cannot be evaluated.
The design also limits what a within-group change can establish. This study is listed as single group, open-label, and unmasked, with allocation not applicable. A change over time in one group can describe what happened among analyzed participants, but without a randomized control group it cannot distinguish an intervention-associated change from other explanations, such as changes in participants' circumstances or measurement over time. No causal comparison should be inferred from the design listing.
The enrollment count is 304, while the overall safety group lists 224 at risk for both serious and other adverse events. Those counts refer to different reported fields; the registry does not explain the difference or give reasons for it. They should not be treated as interchangeable denominators, and the enrollment count alone does not establish how many participants contributed to the primary endpoint. The endpoint population is called the Efficacy Population, but its size and detailed definition are not reported.
For safety, the registry lists 12 participants with serious adverse events and 115 with other adverse events among 224 at risk. These are posted counts, not a comparative estimate against another group. The registry's listed serious adverse event terms each have a reported value of 0.4%, but the record does not give context sufficient to determine event timing, duration of exposure, or whether individual participants experienced more than one event. Deaths are not reported in the registry record.
Any sample-size planning illustration should be separated from observed findings. The stated planning assumptions describe a hypothetical two-arm calculation, while this trial is single group. Those assumptions do not constitute the study's own sample-size justification, observed power, or a substitute for the missing endpoint analysis. The registry record does not report a sample-size justification or interim analyses.
9. Statistical Methods Explained
The record classifies the primary outcome as continuous and specifies a mean and standard deviation. It does not report an analysis result or the statistical procedure used to estimate the change. The explanations below are general statistical context, not a description of methods confirmed for this study.
What does a mean change describe?
In general, a change score compares a participant's follow-up measurement with that participant's baseline measurement. The mean change then averages those participant-level changes among those included in the analysis. It condenses the group's changes into one number, but does not show whether most participants changed similarly or whether the mean reflects a wide range of individual experiences. The registry record does not give the mean change for this endpoint.
The direction of a change depends on how it is calculated and presented. For a pain-intensity score, a decrease would ordinarily represent a lower recorded score, but the numerical result and the registry's sign convention for the change are not reported. It is therefore not possible to state whether the posted endpoint moved up or down, or by how much.
What does the standard deviation add?
In general, the standard deviation describes the spread of individual values around their mean. It is not the same as the standard error, which describes the sampling variability of an estimated mean. A standard deviation can help characterize how heterogeneous participant changes were, while a confidence interval for the mean would address uncertainty in the estimated group average. The registry names standard deviation as the dispersion measure but gives no numerical value for it.
How should uncertainty be assessed?
In general, a confidence interval presents a range of estimates compatible with the observed data under the chosen statistical model and its assumptions. Its width depends on factors such as the amount of information in the analysis and variability in the outcome. A p-value, when used, assesses compatibility of data with a specified null model; it does not measure the size or clinical importance of an effect. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record. There is consequently no reported precision estimate or hypothesis-test result to interpret.
Why does the single-group design matter?
In a randomized comparison, treatment groups can provide a basis for estimating a difference under the design's assumptions. This record instead describes a single-group study with no masking. A baseline-to-follow-up comparison can summarize change in the observed group, but there is no concurrent control group in the listed design to estimate what would have occurred over the same period without the intervention. Open-label participation also means participants and investigators were not masked, as recorded in the registry. These features affect interpretation; they do not reveal the direction or size of any unreported result.
For a continuous endpoint, an analysis might use a model or a direct summary of participant-level change, but the registry does not specify which approach was used. Details such as adjustment for baseline score, handling of repeated observations, covariates, assumptions about the outcome distribution, and treatment of outliers are not reported in the registry record. No particular method should be attributed to the study without that information.
What does over-dispersion mean in general?
Over-dispersion arises when observed variability is greater than a statistical model assumes. In general, if a model understates variability, standard errors may be too small and inferential conclusions can appear more certain than the data warrant. This concept is most relevant to particular outcome models, especially count models; it cannot be assessed from the information reported for this continuous endpoint. The registry does not identify a model or report a dispersion assessment.
What do planning calculations mean?
In general, sample-size calculations illustrate how many participants might be needed under stated assumptions about a target effect, significance level, allocation, and analysis. A planning illustration is not an observed outcome, and it is not observed power. The record's stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It specifies that non-time-to-event figures are participants per arm. The record does not include numerical planning results in the registry record for interpretation, and those two-arm assumptions do not describe the listed single-group trial design.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies one primary outcome measure, change from baseline to week 48 in daily average NRS Pain Intensity Score. It lists 0 analyses. A numerical analysis result, statistical test, confidence interval, and multiplicity adjustment are not reported in the registry record. The number of outcomes alone is not enough to determine whether any analysis plan controlled for multiple testing or how other outcomes may have been handled.
In general, multiplicity arises when several hypotheses or outcomes are tested; repeated testing can increase the chance of at least one apparently unusual result. Statistical plans may address this through prespecified testing hierarchies or adjustments, but the registry does not report such a plan. No adjustment method or testing sequence should be inferred.
The registry names the Efficacy Population for the primary endpoint, but does not report its eligibility rules, size, or analysis-set definition. It does not state whether participants were analyzed according to a particular treatment exposure or whether other analysis populations were used.
Missing-data methods are also not reported in the registry record. The record does not explain how missing baseline or week 48 scores, withdrawals, or incomplete follow-up were handled, or whether any imputation or sensitivity analyses were performed. In general, missing-data choices can affect both the estimated mean change and its uncertainty, particularly when missingness is related to participants' outcomes. Without the analysis details, the extent or direction of any such effect cannot be assessed.
The registry's enrollment count and safety-group counts do not establish the number included in the primary efficacy analysis. No reason for differences between those reported counts is given.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Overall | 12 | 224 | 5.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Overall | 115 of 224 |
Most frequent serious adverse event terms
| Event term | Organ system | Overall |
|---|---|---|
| Bronchitis | Infections and infestations | 1 of 224 |
| Cellulitis | Infections and infestations | 1 of 224 |
| Sepsis | Infections and infestations | 1 of 224 |
| Urosepsis | Infections and infestations | 1 of 224 |
| Syncope | Nervous system disorders | 1 of 224 |
| Status migrainosus | Nervous system disorders | 1 of 224 |
| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 224 |
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 224 |
| Nephrolithiasis | Renal and urinary disorders | 1 of 224 |
| Renal impairment | Renal and urinary disorders | 1 of 224 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Overall |
|---|---|---|
| Nausea | Gastrointestinal disorders | 18 of 224 |
| Upper respiratory tract infection | Infections and infestations | 14 of 224 |
| Back pain | Musculoskeletal and connective tissue disorders | 13 of 224 |
| Headache | Nervous system disorders | 12 of 224 |
| Vomiting | Gastrointestinal disorders | 11 of 224 |
| Diarrhea | Gastrointestinal disorders | 10 of 224 |
| Bronchitis | Infections and infestations | 9 of 224 |
| Constipation | Gastrointestinal disorders | 9 of 224 |
| Depression | Psychiatric disorders | 8 of 224 |
| Nasopharyngitis | Infections and infestations | 7 of 224 |
Serious events with the highest arm-level rate: bronchitis (0.4%), cellulitis (0.4%), sepsis (0.4%), urosepsis (0.4%), syncope (0.4%).
The overall safety group lists 224 participants at risk for serious adverse events and 12 participants affected. For other adverse events, it lists 224 at risk and 115 affected. These are counts as recorded; they do not by themselves describe when events occurred or how long participants were followed. The registry does not report deaths in this record.
The serious adverse event terms listed are bronchitis, cellulitis, sepsis, urosepsis, syncope, and status migrainosus. Each has a reported value of 0.4%. The registry does not provide additional detail in the registry record about event counts by term, timing, duration, severity beyond the serious classification, or recurrence. A listed term should not be interpreted as a comparative risk estimate.
In general, a participant count and an event count are different summaries: one participant may have more than one event. The record's group fields report participants affected, but do not clarify the relationship between participants and total event episodes. The 224 safety-group denominator also should not be assumed to be the primary endpoint analysis population. No comparison group is listed, so these counts do not estimate a difference in safety outcomes between treatments.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase 3, open-label, single-group study evaluated EN3409 in people described as having moderate to severe chronic pain requiring continuous around-the-clock opioid analgesia for an extended period. Its primary endpoint was change from baseline to week 48 in daily average NRS Pain Intensity Score. It also posts overall counts for serious and other adverse events.
Those design and outcome descriptions do not establish the numerical result of the primary endpoint. The mean change, standard deviation, confidence interval, and p-value are not reported in the registry record, and the record lists 0 analyses. It is therefore not possible to describe the amount, direction, or precision of a change in pain scores based on these registry entries. The endpoint's definition is not itself a finding.
Even if a before-and-after change were available, a single-group open-label design would describe change in the studied group rather than provide a randomized estimate of the effect relative to a control. Changes over time may have multiple explanations, and the listed design does not separate them through a concurrent randomized comparator.
The safety figures describe the posted overall group counts, not a treatment comparison. They do not establish event timing, duration of exposure, or a rate over a specified follow-up period. Deaths are not reported in the registry record, which is different from a report that no deaths occurred.
General statistical interpretation requires both an estimate and information about its uncertainty, alongside the design and analysis population. Here, the registry supplies the endpoint definition and some safety counts but not the primary analysis result or key analysis details. Conclusions about efficacy, precision, or comparative safety cannot be drawn from the missing analyses.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why study design and outcome reporting must be read together. The registry describes a phase 3 study and a clearly named continuous primary endpoint, but the design is single group and open-label. A reader therefore needs to distinguish a within-group change question from a randomized treatment-comparison question. They answer different statistical questions.
The endpoint is a mean change in a daily average pain score at week 48, with standard deviation named as the measure of spread. Those choices indicate the intended form of summary, but summaries cannot be interpreted without the actual estimate, the number analyzed, and information about uncertainty. The registry lists 0 analyses, leaving the principal numerical result unavailable in this record.
The safety counts also illustrate why denominators and analysis populations matter. Enrollment is 304, while the listed safety group has 224 at risk. The record does not explain the difference, and it does not state how many participants contributed to the efficacy endpoint. Those counts must remain tied to the populations with which they are reported rather than being treated as interchangeable.
Finally, planning calculations and observed results serve different purposes. General sample-size illustrations depend on assumptions and do not describe what happened in the trial. The stated planning assumptions refer to equal allocation between two arms, whereas the listed trial is single group. Keeping these distinctions clear prevents planning quantities from being mistaken for findings or for evidence of a controlled comparison.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record does not report the primary endpoint estimate, its standard deviation, a confidence interval, or a p-value. It lists 0 analyses, so the primary outcome cannot be interpreted numerically. The outcome's stated population is the Efficacy Population, but its size, inclusion rules, and relationship to the enrolled participants are not reported.
The single-group, open-label design has no listed control arm and no masking. It can describe outcomes within the study group, but it does not provide a randomized comparison with another treatment or a control condition. The record does not report enough analysis detail to assess adjustment, repeated-measure methods, assumptions, or sensitivity analyses.
Missing-data handling, participant withdrawals, and completeness of week 48 measurements are not reported in the registry record. The relationship between the enrollment count of 304 and the safety group's 224 participants at risk is also not explained. The record does not report the duration of safety follow-up for each participant or provide a detailed accounting of exposure.
Deaths are not reported in the registry record. The listed serious adverse event terms have values of 0.4%, but the registry entries do not give event timing or clarify the number of episodes per participant. A sample-size justification and interim analyses are not reported. The stated planning assumptions are not a description of the trial's own design, which is listed as single group.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Long-term Open-Label Safety Study to Evaluate EN3409 — NCT01755546.
- Registry record last updated 2018-10-18; status last verified 2018-03.
- Results first posted 2018-09-12.
- 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.
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18. Record Summary
NCT01755546 is a completed phase 3, open-label, single-group study of EN3409, sponsored by BioDelivery Sciences International. Enrollment is 304. The registry lists low back pain, osteoarthritis, and neuropathic pain, and describes the intervention as buprenorphine HCI buccal film at doses ranging from 300-900 mcg twice daily.
The primary endpoint is change from baseline to week 48 in daily average NRS Pain Intensity Score in the Efficacy Population. The registry specifies a mean and standard deviation but does not report numerical endpoint results; it lists 0 analyses. The overall safety group lists 224 at risk, 12 affected by serious adverse events, and 115 affected by other adverse events. Deaths are not reported in the registry record.