Phase 1b Study of DCR-AUD in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1b Study of DCR-AUD in Healthy Volunteers (NCT05845398), a randomized phase 1 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This was a Phase 1b, randomized, double-blind, placebo-controlled, parallel-group study of repeat-dose DCR-AUD in healthy volunteers who were social drinkers. The registry records enrollment of 16 and lists the study status as completed. The recorded study start was 2023-01-29, and the primary completion date was 2023-08-22. These dates describe the registry timeline; they do not establish when all analyses were completed or reported.

Participants assigned to DCR-AUD received multiple subcutaneous doses. Participants assigned to placebo received multiple subcutaneous doses of a placebo comparator, with volume to match the active single dose. The registry describes assessment visits through Week 24 and up to 10 Ethanol Interaction Assessments. These assessments were intended to examine how the body was affected by DCR-AUD during alcohol interaction testing.

The stated goals covered safety and tolerability, pharmacokinetics, and pharmacodynamics. Listed secondary outcomes include symptom responses during ethanol interaction assessments; plasma concentration measures for DCR-AUD and acetaldehyde; and changes from baseline in heart rate and facial skin temperature. The record lists 14 outcome measures, but the analysis count is 0. It does not report the detailed allocation procedure, the dose schedule, the specific alcohol exposure procedure, or a full statistical analysis plan. The design and aims should therefore be distinguished from results: the registry gives safety counts, but does not provide a complete set of analyses for the listed outcomes.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: In this trial total 16 healthy participants were randomized in 3:1 ratio to DCR-AUD or placebo.

Overall Study

Analysis population for the primary outcome, as defined in the registry: SP: All participants randomized to study intervention and who receive at least 1 dose of DCR-AUD or placebo.

5. Baseline Characteristics

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

Population: Safety Population (SP): All participants randomized to study intervention and who receive at least 1 dose of DCR-AUD or placebo.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), measured over From Day 1 up to 24 Weeks.

The primary outcome is the number of participants with treatment-emergent adverse events and serious adverse events from Day 1 up to 24 Weeks. A treatment-emergent adverse event is an event that begins or worsens in severity after study drug administration. The registry’s definition includes unfavorable or unintended signs, symptoms, diseases, or abnormal laboratory findings temporally associated with study intervention, whether or not considered related to it. A serious adverse event is defined by consequences such as death, a life-threatening event, inpatient hospitalization or its prolongation, persistent or significant disability, a congenital anomaly or birth defect, or another important medical event.

Counting participants who experience events is a descriptive safety measure. It records whether participants were affected, rather than how many total event episodes occurred or how severe every event was. The serious-event category helps distinguish events meeting the registry’s seriousness criteria from other adverse events. Neither category, by itself, establishes that the study drug caused an event: the definition is based on timing and seriousness, and the record does not state that every event was judged related to treatment.

The endpoint is relevant to an early-phase study because safety and tolerability are among its stated aims. However, counts alone do not describe event timing, duration, recurrence, severity beyond the serious classification, or clinical attribution. The record does not report a single inferential comparison for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-blind, parallel-group study. Randomization is intended, in general, to assign participants to interventions by chance and reduce systematic differences between groups at the start of a trial. Double blinding is intended to limit the influence of treatment knowledge on participant experience, care, and outcome assessment. These are general purposes of the design features; the detailed randomization and masking procedures are not reported in the registry record.

What does a participant count represent?

The primary outcome is expressed as the number of participants with treatment-emergent adverse events and serious adverse events. A participant count treats each participant as affected or not affected for the specified outcome category and observation period. It is different from a total event count: a participant may experience more than one event, but a count of participants does not reveal the number of episodes. The record does not provide event-level detail sufficient to describe recurrence, timing, duration, or severity for each non-serious event.

The endpoint population is defined as all participants randomized to study intervention who received at least 1 dose of DCR-AUD or placebo. This is a treatment-exposed population definition, rather than a statement that every randomized participant is included regardless of whether they received treatment. The safety record gives participants at risk by group. The registry does not report how many participants were randomized but did not receive a dose, or provide a separate accounting of exclusions from the primary outcome population.

Why does uncertainty matter?

A confidence interval is a general statistical tool for expressing the precision of an estimate. It gives a range of values compatible with the data under the method’s assumptions; it is not a guarantee that the true value lies in the range. Small samples commonly produce imprecise estimates, even when the observed counts are easy to describe. The registry does not report confidence intervals for the safety counts, so readers cannot use the record to assess their interval-based precision.

An inferential comparison would require a defined estimand and analysis method. For a binary outcome, those choices can include how to define the event, the analysis population, the comparison measure, and how to handle sparse data. General methods may behave differently when event counts or group sizes are small. The record does not report a method for testing or estimating a treatment contrast, so no comparative statistical conclusion should be inferred from the raw counts.

What does double blinding contribute?

In general, blinding can reduce bias when outcomes involve judgment or when expectations might affect reporting. It cannot remove all sources of bias, and it does not replace complete outcome collection or transparent analysis. The registry identifies the study as double-blind but does not describe who was masked, how the masking was maintained, or whether masking was assessed.

How should the many outcomes be viewed?

The registry lists 14 outcome measures, including safety, pharmacokinetic, pharmacodynamic, and alcohol-interaction measures. When a study assesses multiple outcomes, multiplicity is a general concern: testing or interpreting many results can increase the chance that some findings appear notable by chance. Statistical plans may address this through prespecified outcome hierarchies, adjustment procedures, or a clearly exploratory interpretation. Such procedures are not reported in the registry record. The analysis count is 0, and no adjustment or testing strategy is described.

The primary outcome has several categories or time points and was not reduced to one comparison in the registry record. This matters because a broad endpoint label does not itself specify which contrast, event definition, or time point should drive an inferential conclusion. The posted adverse-event counts provide descriptive information, but they do not supply the missing analysis specification.

What can be concluded from the posted counts?

The available safety figures describe the recorded participants with serious events, other events, and deaths in each group. They do not provide a model-based estimate, adjustment for baseline characteristics, or an uncertainty interval. General statistical interpretation distinguishes a descriptive observation from evidence about a broader population: the former reports the study data, while the latter depends on assumptions, design, and analysis. The registry record does not report enough analytical detail to make that broader comparative assessment.

Other listed outcomes include drug and acetaldehyde concentration measures, symptom responses during ethanol interaction assessments, and changes from baseline in heart rate and facial skin temperature. These measures generally require outcome-specific definitions and analysis choices. For example, concentration measures describe exposure over time or at a measured point, while a change-from-baseline outcome compares a follow-up measure with a starting measure. Those general descriptions do not establish any result for this study. Numerical results and methods for these secondary outcomes are not reported in the registry record.

The record’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. No resulting planning estimates are included in the record. Such illustrations, when reported, are planning calculations rather than observed evidence or observed power. The registry does not report the trial’s own sample-size justification, so the planning assumptions should not be treated as its design rationale.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures, spanning adverse events, pharmacokinetics, pharmacodynamics, ethanol interaction symptoms, and physiological changes. Assessing multiple outcomes raises a general multiplicity issue: without a prespecified strategy, repeated testing can make chance findings more likely to be highlighted. Common general approaches include prioritizing outcomes in advance, adjusting inference, or explicitly treating secondary results as exploratory. The multiplicity strategy for this study is not reported in the registry record.

The analysis count is 0, and the record does not provide a statistical analysis plan, inferential methods, or a complete set of outcome results. It also does not report whether any interim analyses were conducted. These details should not be inferred from the study’s phase or stated objectives.

Missing-data methods are not reported in the registry record. There is no description of how missing outcome observations, withdrawals, or incomplete follow-up were handled, nor a reported sensitivity analysis. The record states that primary outcome observation runs from Day 1 up to 24 Weeks, but that timeframe alone does not show whether every participant contributed complete follow-up.

The primary outcome population is defined as randomized participants who received at least 1 dose of DCR-AUD or placebo. The safety figures also give participants at risk by group. The registry does not report a separate analysis population for each secondary outcome, an intention-to-treat analysis, or the handling of participants who did not receive treatment. These omissions limit assessment of how closely the reported counts reflect all randomized participants and how robust analyses might be to 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 registry reports 0 serious adverse events among 12 participants at risk in the DCR-AUD group and 0 among 4 participants at risk in the placebo group. Deaths were 0 in each group. For other adverse events, the record reports 11 affected participants in the DCR-AUD group and 3 in the placebo group. These are participant counts, not counts of all event episodes.

The registry defines a treatment-emergent event by its timing: it begins or worsens after study drug administration. This does not by itself establish that the intervention caused the event. Seriousness is defined by specified outcomes such as death, life-threatening events, hospitalization, significant disability, congenital anomaly or birth defect, or another important medical event. The record does not list serious-event terms.

The difference in group sizes is important context when reading raw counts. The counts do not include uncertainty intervals or a statistical comparison, and the record does not report event-level timing, duration, severity details for other events, or treatment attribution. No serious events recorded in this study is a description of these observed participants and follow-up, not a guarantee about other settings or populations.

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

The registry record documents a completed, randomized, double-blind, placebo-controlled Phase 1b study of repeat-dose DCR-AUD in healthy volunteers who were social drinkers. Its stated aims were to assess safety and tolerability, pharmacokinetics, pharmacodynamics, and symptoms during alcohol interaction assessments. The posted safety data show the recorded participant counts for serious and other adverse events and deaths in the two groups.

Those observations do not establish a causal treatment effect. The event definitions are based on occurrence and timing, and the record does not report that every event was judged related to study intervention. The counts also do not provide a measure of uncertainty or a formal comparison. With small group sizes, the observed counts offer limited precision about event occurrence beyond the participants enrolled and followed.

The absence of recorded serious adverse events and deaths in the listed groups does not establish that such events cannot occur. It reflects the safety observations reported for this study and its stated follow-up period. It cannot, on its own, determine safety in people with Alcohol Use Disorder or in other populations, because the stated participants were healthy volunteers who were social drinkers.

The study’s aims and listed outcomes should not be mistaken for findings. The registry lists pharmacokinetic, pharmacodynamic, symptom, heart-rate, and facial-skin-temperature outcomes, but numerical results for these measures are not reported in the registry record. The record also does not provide a single reduced comparison for the primary endpoint or describe an inferential analysis.

Accordingly, the posted data support a limited descriptive reading of the recorded safety counts. They do not establish whether DCR-AUD changes adverse-event risk, whether it affects alcohol-related symptoms, or how it behaves in the body. Those questions require results and analyses that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a trial’s aims, its measured outcomes, and the evidence actually reported. The registry describes broad safety, pharmacokinetic, and pharmacodynamic objectives, but the available result detail is concentrated in safety counts. A trial can list many outcomes without the registry record supplying an analysis for each one.

The event counts also illustrate why denominators and precision matter. Raw participant counts are meaningful descriptions, but group sizes are small and unequal in the safety record. Without confidence intervals or a stated comparative method, readers cannot assess the precision of a contrast from the registry record. The absence of recorded serious events is a relevant observation, but not proof of zero underlying risk.

The primary outcome combines treatment-emergent and serious adverse events, while the recorded safety figures separate serious events from other events. That makes it important to distinguish the endpoint’s definition from the specific summaries available. A clear statistical report would ordinarily make the analysis population, outcome definitions, time handling, missing-data approach, and comparative method transparent. Those details are not reported in the registry record.

The record lists 14 outcome measures and 0 analyses. This gap highlights the role of prespecification and multiplicity planning in studies that assess multiple types of outcomes. Without a reported analysis strategy, readers cannot determine how outcomes were prioritized or how any multiplicity was handled. The record’s planning assumptions should also not be mistaken for a report of the study’s design justification or for evidence of observed power.

Overall, the trial’s statistical value in this registry record lies in what it makes visible about early-phase study reporting: descriptive observations can be useful, but their interpretation depends on complete outcome results and analytical context. The available counts should be read narrowly, without extending them to unreported endpoints or broader populations.

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 detailed statistical analysis plan, the randomization procedure, or the operational details of masking. It does not provide an account of whether the planned allocation was maintained or whether there were deviations from the intended study procedures. These omissions limit assessment of potential design and conduct issues.

Although the record gives adverse-event counts by group, it does not provide confidence intervals, an inferential comparison, or a treatment-effect estimate. It does not report event-level detail for the other adverse events, including their timing, duration, severity, or judged relationship to study intervention. Serious-event terms are not listed. Counts therefore cannot characterize the full safety profile.

The stated primary endpoint timeframe is from Day 1 up to 24 Weeks. The record does not explain participant-level follow-up, missing observations, withdrawals, or the handling of incomplete data. It also does not state whether participants who were randomized but did not receive treatment were present or how they would be handled analytically.

The registry lists 14 outcome measures but reports 0 analyses. Numerical results for pharmacokinetic, pharmacodynamic, symptom, heart-rate, and facial-skin-temperature outcomes are not reported in the registry record. The primary outcome was not reduced to one comparison because it has several categories or time points. Procedures for multiplicity and any interim analyses are not reported.

The study population was healthy volunteers who were social drinkers, so the record does not directly describe outcomes in people being treated for Alcohol Use Disorder. The enrollment and group sizes are limited for precise safety estimation, particularly for uncommon events. The record’s planning assumptions do not include reported planning results and are not identified as the trial’s own sample-size justification.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 1b Study of DCR-AUD in Healthy Volunteers — NCT05845398.
• Registry record last updated 2026-01-14; status last verified 2025-12.
• Results first posted 2025-01-03.
• 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

The registry describes NCT05845398, a completed Phase 1b randomized, double-blind, placebo-controlled, parallel-group study of repeat-dose DCR-AUD in healthy volunteers who were social drinkers. Enrollment was 16. The recorded study start was 2023-01-29, and primary completion was 2023-08-22.

The primary outcome counted participants with treatment-emergent adverse events and serious adverse events from Day 1 up to 24 Weeks. The safety record lists 12 participants at risk in the DCR-AUD group and 4 in the placebo group. Other adverse events affected 11 and 3 participants, respectively; serious adverse events were 0 in each group, and deaths were 0 in each group.

The registry lists 14 outcome measures and 0 analyses. It does not report a single reduced primary-outcome comparison, an inferential statistical analysis, or numerical results for the listed secondary outcomes. Multiplicity procedures, missing-data methods, and the study’s own sample-size justification are not reported in the registry record.