Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion (NCT05976646), a randomized phase 1, phase 2 study. The primary outcome is Safety- as Measured by Average Heart Rate (Pulse) at Each Testing Visit.

2. Clinical Question

The registry record frames the project as an initial human study of safety, including possible interactions with an opioid drug such as buprenorphine, and early signals involving negative affect, craving, and opioid withdrawal. These are stated aims, not reported findings. The primary outcome identified in the record is average pulse; it does not provide numerical heart-rate results or a comparison between groups.

The clinical question is therefore narrower than whether Auvelity improves opioid use disorder outcomes. The record does not establish a treatment effect on opioid use, craving, withdrawal, or any other clinical outcome. It identifies placebo as the comparator and heart rate as the primary safety measure, but numerical results for that measure are not reported in the registry record. Other outcome measures are mentioned only as a count, without their names or results.

3. Trial Design

The study is titled as a Phase Ib/2a drug-drug interaction study of dextromethorphan with bupropion, also named Auvelity, as an adjunctive treatment for buprenorphine/naloxone for opioid use disorder. Its stated overall goal is to collect initial human data on safety and early efficacy signals among people with opioid use disorder who are currently receiving medication treatment with buprenorphine.

The design is randomized, double-masked, and parallel. Participants were assigned to Auvelity or placebo. The placebo is described as identical capsules administered orally at the same time periods as the test product. The Auvelity arm is described as receiving an oral combination of dextromethorphan with bupropion. The record does not describe the schedule or duration of dosing beyond those details.

Enrollment is recorded as 18. For the primary outcome, the registry describes the assessed population as all participants who started the study and gives 6 for the placebo group and 12 for the Auvelity group. The study status is completed. The recorded start date is 2023-09-18, and the primary completion date is 2025-07-09. The sponsor is Virginia Commonwealth University.

The study includes five outcome measures, but the record does not name or describe all of them. It identifies no statistical analyses in the analysis count. Details of random sequence generation, allocation concealment, the masking procedures, dose schedule, and the statistical analysis plan are not reported in the registry record. The record also does not explain how the Phase Ib/2a components were organized or whether any design features changed during conduct.

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

Analysis population for the primary outcome, as defined in the registry: all participants who Started the study (i.e., 6 and 12 participants in each Arm/Group, respectively) were assessed at each time point reported in the data table.

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 Safety- as Measured by Average Heart Rate (Pulse) at Each Testing Visit, measured over Baseline and Day 8 (PK testing visits).

The primary outcome is safety measured by average heart rate, also called pulse, at baseline and Day 8 during pharmacokinetic testing visits. The unit is beats per minute, and the outcome is specified as a mean with standard deviation. The stated population consists of all participants who started the study; the record identifies 6 in the placebo group and 12 in the Auvelity group as assessed at each reported time point.

Heart rate is a continuous measure. A mean describes the group’s average value, while a standard deviation describes how much individual measurements vary around that average. Considering both can give a sense of the group result and its variability. The registry description says pulse provides real-time, objective data and can serve as a baseline indicator for detecting irregularities and monitoring stress and fatigue. It also describes a healthy resting heart rate for most adults as 60-100 beats per minute. That general reference does not, by itself, define the study’s treatment comparison or establish a clinical outcome.

The record does not report the mean or standard deviation for either group at either time point. It also does not report a change from baseline, a between-group estimate, or a confidence interval. Consequently, the stated endpoint and measurement schedule can be described, but the heart-rate results and their precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods below explain how the listed design and outcome types are generally interpreted. They do not add results that are absent from the registry record.

What does a mean and standard deviation describe?

For a continuous measure such as pulse in beats per minute, the mean is the arithmetic average across the observed measurements. It summarizes the group’s central value, but does not show whether every participant had a similar measurement. The standard deviation describes the spread of measurements around the mean. A larger spread means observations are more dispersed; a smaller spread means they are closer to the average.

Mean and standard deviation are descriptive statistics. On their own, they do not show whether groups differ beyond what might be expected from sampling variation. To estimate a group contrast, an analysis would need to specify the comparison being made, such as a difference between groups at a time point or a difference in change from baseline. The registry record does not report such an estimate for heart rate.

Why might the analysis account for baseline values?

In general, measurements collected at baseline can help describe participants before treatment and can be used in an analysis of subsequent measurements. A comparison of Day 8 values alone answers a different statistical question from a comparison of change from baseline. An adjusted model may also account for baseline values, but its interpretation depends on the model and prespecified analysis. The registry record names baseline and Day 8 measurements but does not report which comparison or model was used.

What does randomization contribute?

In general, random assignment aims to make treatment groups comparable, on average, with respect to measured and unmeasured factors at the time of assignment. It does not guarantee that groups will be balanced in a small study. The registry labels this study randomized, but the sequence-generation and allocation-concealment methods are not reported in the registry record. The group sizes recorded for the primary outcome are 6 for placebo and 12 for Auvelity; the record does not explain the assignment ratio or any difference between enrollment and assessment.

What does masking contribute?

Double masking generally means that more than one relevant party is unaware of assigned treatment, which can reduce the risk that expectations influence care, reporting, or assessment. The record labels the study double-masked and says placebo capsules were identical to the test product. It does not specify which parties were masked, how masking was maintained, or whether masking was assessed. Those procedural details are not reported in the registry record.

How should uncertainty be considered?

A confidence interval is a statistical range expressing uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but neither width nor location can be assessed without a reported estimate and interval. The registry record does not report a confidence interval for the primary outcome. A p-value, if reported, would address a different question about compatibility with a specified null model; it would not by itself describe the size or clinical importance of a difference. No p-value for the primary outcome is reported in the registry record.

What does over-dispersion mean for count outcomes?

In general, count data can vary more than a simple statistical model assumes. This is called over-dispersion. If it is present and not handled appropriately, standard errors and confidence intervals can be misleading. It is not possible to assess over-dispersion from the adverse-event counts alone, and the registry record does not report a count-data model or an inferential analysis of adverse events. For these reported safety figures, the most direct reading is descriptive: the record gives the number at risk and the number with events in each category.

How should planning calculations be read?

Sample-size illustrations are planning tools rather than observations from a trial. The stated planning approach uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. For time-to-event outcomes, the stated approach concerns total events; for other outcomes, it concerns participants per arm. These assumptions describe a planning illustration, not the trial’s own design or an observed-power calculation. The registry record does not report a sample-size justification or the actual numerical planning illustrations, so no planning estimate can be interpreted from the record.

More generally, a planning calculation depends on the outcome, assumed effect, variability, allocation, analysis, and desired power. Changing an assumption changes the planning result. Such illustrations do not show that a study had a particular probability of detecting an effect after the data have been observed, nor do they establish whether a treatment effect exists.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, but only the primary heart-rate outcome is described in the record. The other outcome measures, their time points, and their analysis details are not reported in the registry record. The record does not identify a testing hierarchy, a multiplicity adjustment, or a plan for interpreting several outcomes. It also does not state whether interim analyses were planned or conducted; those details are not reported in the registry record.

In general, when several outcomes or comparisons are tested, the chance of obtaining at least one apparently notable result by chance can increase. Prespecified outcome priorities and appropriate methods can help readers interpret a collection of tests. The absence of a reported multiplicity plan does not establish that no such plan existed; it means the registry record does not document one.

The analysis count is recorded as 0. This means no analyses are reported in the registry record’s analysis information; it does not establish what analyses may have been conducted outside that record. The record does not describe a primary analysis population beyond saying that all participants who started the study were assessed for the reported heart-rate time points. It does not state whether the analysis followed randomized assignment or used another population definition.

Missing-data methods, the amount of missing outcome information, reasons for missingness, and any imputation or sensitivity analyses are not reported in the registry record. The record also does not explain how participants with incomplete baseline or Day 8 measurements would be handled. These omissions make it difficult to assess whether the reported safety counts and any unreported outcomes were affected by missing observations.

11. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety information separates serious adverse events, other adverse events, and deaths. In the placebo group, 0 of the 6 participants at risk had a serious adverse event, and 5 of the 6 had an event in the other-adverse-event category. In the Auvelity group, 0 of the 12 participants at risk had a serious adverse event, and 9 of the 12 had an event in the other-adverse-event category. Deaths are recorded as 0 in each group.

These counts describe participants with events, as recorded in the registry. They do not report the number, nature, timing, duration, or severity of individual events in the other-adverse-event category. The registry record lists no top serious adverse-event terms. It does not report a statistical comparison, confidence interval, or analysis of differences between groups. The counts should therefore be read descriptively rather than as evidence that the groups had equivalent safety profiles.

The numbers at risk are the denominators recorded for these safety categories. They are not necessarily a complete account of exposure or follow-up, because those details are not reported in the registry record. The record also does not explain how adverse events were collected or whether participants could contribute more than one event to a category. No conclusions about event causes or treatment effects can be drawn from these counts alone.

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

The record establishes that a randomized, double-masked, parallel Phase Ib/2a study of Auvelity versus placebo was completed in the setting of buprenorphine treatment for opioid use disorder. It identifies average pulse at baseline and Day 8 as the primary safety outcome and gives adverse-event counts by group. These details describe the study’s design and the safety information posted in the registry.

The record does not report the primary heart-rate means, standard deviations, changes, or between-group estimates. It therefore does not show the size or precision of any heart-rate difference. The adverse-event counts can be read as descriptive observations, but no inferential comparison is reported. Neither these counts nor the study’s completion status establish that treatments were equivalent or that a treatment caused or prevented an event.

The stated aims include safety, possible interaction with an opioid drug, and early signals involving negative affect, craving, and opioid withdrawal. A statement of aims does not establish that those outcomes changed. The registry does not report the names and findings of the other outcome measures. It also does not provide results that would support conclusions about opioid use or broader treatment effectiveness.

The study’s randomized and double-masked labels are relevant design features, but they cannot resolve the uncertainty created by missing outcome summaries and analysis details. The record does not report the statistical plan, methods for missing data, or confidence intervals. The findings that can be described are therefore limited to the design information and the posted safety counts. Any further conclusion about comparative effects would require results not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable as an early-phase, randomized comparison focused on safety and drug-drug interaction questions in people receiving buprenorphine treatment. Early-phase studies can generate initial human observations that help define questions for later research. The registry’s stated aims include safety and early efficacy signals, but aims should be distinguished from findings: the record does not report the primary heart-rate summaries or results for the other outcomes.

The design also illustrates why an outcome definition and its analysis matter. Average heart rate is measured at baseline and Day 8, but those two time points could support different statistical questions, such as comparing groups at Day 8 or comparing changes over time. The registry record does not identify which comparison was used. Without that information and the corresponding estimates, readers cannot evaluate the magnitude or precision of a treatment contrast.

The recorded group sizes for the primary outcome are 6 for placebo and 12 for Auvelity. In a study with these group sizes, estimates may be sensitive to the observations collected, and uncertainty is important to interpret. This general point does not determine the study’s actual uncertainty; numerical outcome estimates and intervals are not reported in the registry record.

Finally, the adverse-event counts show why descriptive safety data should not be overinterpreted. Counts provide a record of participants with events, but they do not reveal event-level detail or establish a comparative effect. Transparent reporting of outcome summaries, analysis methods, and uncertainty would be needed to judge what the study contributes beyond its design and posted event counts.

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 most important limitation for interpreting results is that the registry record does not report numerical results for the primary outcome. Although it specifies mean heart rate, standard deviation, and measurement at baseline and Day 8, it gives no group summaries or estimated comparison. The precision of any difference is therefore not assessable.

The record provides limited detail about the remaining outcome measures. It states that there are five outcome measures, but does not identify the other measures or report their results. This prevents assessment of the full set of safety and early efficacy signals described in the study summary. The record does not report details of the statistical analysis plan, multiplicity handling, missing-data methods, or analysis populations beyond the primary outcome population description.

The group sizes recorded for the primary outcome are unequal: 6 for placebo and 12 for Auvelity. The record does not explain why the groups differ in size, whether this reflects the allocation plan, or whether participants lacked outcome data. It states that all participants who started the study were assessed at each reported time point, but does not provide participant-level flow or reasons for any unavailable measurements.

The safety information is also limited. The registry gives counts for serious and other adverse events and deaths, but does not describe the other events, their timing, or their severity. It does not report exposure duration, event-collection procedures, or a statistical comparison of safety outcomes. Randomization and double masking are recorded, but the methods used to implement them are not reported in the registry record. These limitations constrain interpretation of both the primary safety question and the broader aims.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion — NCT05976646.
• Registry record last updated 2026-08-19; status last verified 2026-07.
• Results first posted 2026-08-19.
• 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.

18. Record Summary

NCT05976646 is a completed, randomized, double-masked, parallel Phase Ib/2a study sponsored by Virginia Commonwealth University. It compares oral Auvelity with placebo as an adjunct to buprenorphine/naloxone treatment for opioid use disorder. Enrollment is recorded as 18; the primary outcome population is described as all participants who started the study, with 6 in the placebo group and 12 in the Auvelity group.

The primary outcome is average heart rate at baseline and Day 8 during pharmacokinetic testing visits. Numerical results for that outcome are not reported in the registry record. The record reports 0 serious adverse events and 0 deaths in each group, with other-adverse-event counts of 5 for placebo and 9 for Auvelity. Statistical analyses, detailed results for the other outcome measures, and further methods for missing data and analysis are not reported in the registry record.