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 Randomized, Double-Blind, Placebo-Controlled Pilot Study on the Safety and Effectiveness of LUCEMYRA During an Opioid Taper in Treatment of Withdrawal (NCT04070157), a randomized phase 2 study. The primary outcome is Number of Treatment Emergent AEs and SAEs.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04070157 |
| Phase | Phase 2 |
| Condition | Opioid Withdrawal (Disorder) |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | USWM, LLC (dba US WorldMeds) |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned subjects with chronic non-cancer pain and opioid withdrawal. The registry lists opioid withdrawal as the condition. It does not report further eligibility details or the characteristics of the enrolled participants.
Intervention
The intervention was lofexidine, named in the registry as LUCEMYRA. The study title and brief description place its use during an opioid taper. Dose, dosing schedule, and other treatment details are not reported in the registry record.
Comparator
The comparator was placebo. The record identifies both study arms but does not describe their treatment procedures or provide additional arm-level details.
Primary question
The primary outcome was the number of participants with treatment-emergent adverse events and serious adverse events from Day 1 through Day 28. The study’s stated broader aim was to test whether LUCEMYRA could reduce withdrawal symptoms and help more participants reduce opioid dose compared with placebo. The posted record does not provide a single comparative primary-outcome estimate or a reported efficacy result.
These questions are related but not interchangeable. A safety endpoint describes adverse events during a defined period; withdrawal scores and taper completion address symptoms and taper progress. The registry lists secondary outcomes for these areas, including withdrawal scales, successful completion of dose reductions, and time to study-drug discontinuation. Their presence in the outcome list does not establish that results were observed, analyzed, or favorable in either arm.
3. Trial Design
This was a Phase 2 randomized, quadruple-masked, parallel-group study comparing lofexidine with placebo. The official title describes a pilot study of opioid withdrawal during an opioid taper in subjects with chronic non-cancer pain. Randomization means that assignment was intended to use a chance-based process; the registry does not report the sequence-generation method or allocation-concealment procedures. The record identifies the masking level as quadruple but does not specify which participant, investigator, or other roles were masked.
The registry reports enrollment of 4. It lists the study status as terminated, a start date of 2019-08-02, and a primary completion date of 2019-11-27. It does not report the reason for termination, whether enrollment reached a planned target, or the number of participants who completed treatment or follow-up. The record also does not describe the taper schedule, treatment duration beyond the primary endpoint’s Day 1 through Day 28 timeframe, or the clinical setting.
The arms are identified as Lofexidine and Placebo, but their arm descriptions are blank. Beyond the study title and brief summary, details such as dose, medication administration, tapering rules, permitted concomitant treatments, and treatment adherence are not reported in the registry record. The study lists 24 outcome measures and 0 analyses. The listed secondary measures cover taper completion, withdrawal scales, global impressions, study-drug discontinuation, and use of non-opioid concomitant medications for withdrawal symptoms. Listing an outcome does not itself establish that results are available for it.
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
| Stage | Lofexidine | Placebo |
|---|---|---|
| STARTED | 1 | 3 |
| COMPLETED | 0 | 2 |
| NOT COMPLETED | 1 | 1 |
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.
| Characteristic | Unit | Lofexidine | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 3 | 4 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 3 | 4 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 0 | 1 | 1 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 0 | 3 | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 1 | 3 | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Treatment Emergent AEs and SAEs, measured over Day 1 through Day 28.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with treatment-emergent adverse events and serious adverse events from Day 1 through Day 28. Its unit is participants, so the endpoint concerns how many participants experienced events, rather than the total number of individual event episodes. The registry record does not provide a fuller definition of treatment-emergent events, the method used to classify seriousness, or the rules for attributing events to study treatment.
Safety outcomes are used to describe unwanted events observed during a study period and to compare the recorded experience between assigned groups. A defined timeframe helps clarify which events contribute to the endpoint. However, an event occurring after treatment begins is not automatically caused by that treatment; causal attribution requires clinical and study-specific assessment. The posted counts alone do not provide that assessment.
The registry’s primary endpoint is expressed as a number of participants, but the record does not present a single primary-outcome comparison or an inferential estimate. The posted safety counts separately report participants at risk and participants affected for serious and other adverse events. They should be read as small descriptive counts, not as a definitive estimate of a treatment difference. The registry does not report a prespecified analysis method, confidence interval, or hypothesis test for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The recorded safety counts are highly limited by the enrollment of 4. In the lofexidine group, 0 of 1 participant at risk had a serious adverse event, and 0 of 1 had another adverse event. In the placebo group, 0 of 3 participants at risk had a serious adverse event, while 3 of 3 had another adverse event. No deaths were reported in either group. The record does not list serious adverse-event terms.
These are descriptive counts from groups of very different size. They do not establish that one treatment caused more or fewer events. In particular, a count of 0 among 1 participant provides little information about the range of event experiences that could occur in a larger group. The same caution applies to the placebo count: the observation that all 3 participants at risk were recorded with other adverse events does not establish how often such events would occur in a broader population or whether treatment caused them.
The primary outcome combines treatment-emergent adverse events and serious adverse events, but the registry record does not reduce it to one comparative result. It provides separate safety counts rather than an adjusted or unadjusted estimate with uncertainty. The record lists 0 analyses, so no analysis results, p-values, or confidence intervals are reported. There is also no single posted efficacy result for withdrawal symptoms or taper success in the registry record for this trial.
The registry status is terminated. That status is relevant context, but the reason for termination and its relationship to the observed counts are not reported in the registry record. The record also does not say whether data collection ended as planned, whether participants discontinued, or whether outcome information was missing.
Overall, the posted results describe a very small set of safety observations. They do not support a precise comparison between lofexidine and placebo, and they do not resolve the broader question of withdrawal symptoms or taper completion. Absence of recorded serious events in these counts should not be interpreted as proof that serious events cannot occur.
9. Statistical Methods Explained
What does randomization contribute?
General statistical explanation: Randomization assigns participants to study groups using chance, with the aim of reducing systematic differences between groups at assignment. It does not guarantee that groups will be similar in every characteristic, especially when enrollment is very small. The registry identifies this trial as randomized but does not report how the random sequence was generated, how assignments were concealed, or whether any stratification was used. Those details therefore cannot be assessed from the registry record.
The parallel design means participants are assigned to one study arm rather than crossing between treatments. The record names lofexidine and placebo and describes the study as quadruple-masked. Masking is intended to limit the influence of knowledge of assignment on participant experience, clinical decisions, or outcome assessment. The registry does not identify the four roles covered by its masking label or describe how masking was maintained.
What does a participant-count endpoint mean?
General statistical explanation: A participant-count endpoint records how many people experienced a defined event, rather than how many event episodes occurred. One person may experience more than one event, but a participant-based count does not necessarily distinguish repeated episodes unless the outcome definition says it does. The primary outcome is described in terms of participants with treatment-emergent adverse events and serious adverse events. The record does not provide enough detail to determine how a participant with multiple events was counted in the primary endpoint or how the separate categories were combined.
For a group comparison, counts are usually interpreted in relation to the number of participants who could have experienced the outcome. The posted safety results include those at risk and those affected. With only 1 participant at risk in the lofexidine group and 3 in the placebo group, each individual observation has substantial influence on the group description. The record gives no confidence intervals or model-based estimates to express uncertainty around a treatment contrast.
How should uncertainty be understood?
General statistical explanation: A confidence interval is a range of values compatible with the observed data under a specified statistical method. It can communicate the precision of an estimate, while a point estimate alone may conceal substantial uncertainty. No confidence interval is reported for the primary endpoint in the registry record. Without a reported comparative estimate and its uncertainty, the magnitude and precision of any between-group difference cannot be assessed from these results.
Small samples also make statistical tests and estimates sensitive to individual observations. A lack of a reported statistically significant result would not establish that groups are equivalent; in this case, the registry does not report a primary comparison or a test result at all. No equivalence or non-inferiority margin is reported, and no conclusion of equivalence can be drawn.
What can the analysis record establish?
The registry lists 24 outcome measures and 0 analyses. This means the record, as represented, does not supply analysis results for those listed measures. It does not identify an analysis population, explain how participants with incomplete observations were handled, or specify covariate adjustment. These details are not reported in the registry record. The results available for safety remain descriptive counts; there is no reported analysis that turns those counts into a treatment-effect estimate.
General statistical explanation: Repeated outcomes, such as scores collected across multiple visits, require methods that account for measurements from the same participant being related to one another. Event outcomes can also require careful handling when participants have different observation times. Over-dispersion is a general concern when count data vary more than a simple statistical model expects; a suitable method may need to account for that extra variability. These are general considerations, not descriptions of methods used in this trial. The registry does not report the planned or performed statistical methods for the listed withdrawal scales, taper outcomes, or safety endpoint.
The record does not report a sample-size justification or a planned target enrollment. Any sample-size illustration based on an observed effect is a planning aid under stated assumptions, not observed power and not evidence that the trial could detect a clinically important difference. No such design justification is reported in the registry record. With the small enrollment recorded, the available counts should be read as limited observations rather than as a precise estimate of treatment effects.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 24 outcome measures, including the primary safety outcome and secondary measures of taper completion, withdrawal symptoms, global impressions, study-drug discontinuation, and use of non-opioid concomitant medications. When a study considers multiple outcomes, timepoints, or comparisons, the chance of at least one apparently notable result can increase if many tests are performed. General statistical explanation: A prespecified multiplicity strategy can define which results are confirmatory and how statistical error is controlled across tests.
The registry record does not report a multiplicity plan, a hierarchy among secondary outcomes, or methods for repeated comparisons. It also lists 0 analyses, so there are no reported analysis results from which to assess how multiple outcomes were handled. The outcome list alone does not establish that each measure was collected or analyzed.
The record does not report an analysis population, the number of participants with outcome data at each assessment, or how missing observations were handled. It does not state whether the analyses were intended to follow randomized assignment, include only participants who received treatment, or use another population definition. The reason for termination and any effect on outcome completeness are also not reported in the registry record.
General statistical explanation: Missing data can affect interpretation when the chance that an observation is missing is related to a participant’s condition, treatment experience, or outcome. An analysis that excludes missing observations may not represent all randomized participants if missingness is informative. Without information on completion, missingness, and the planned analysis population, the extent of any such concern cannot be assessed for this trial.
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 |
|---|---|---|---|
| Lofexidine | 0 | 1 | 0.0% |
| Placebo | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Lofexidine | 0 of 1 |
| Placebo | 0 of 3 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Lofexidine | 0 of 1 |
| Placebo | 3 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Lofexidine | Placebo |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 0 of 1 | 1 of 3 |
| Sneezing | Respiratory, thoracic and mediastinal disorders | 0 of 1 | 1 of 3 |
| Rash | Skin and subcutaneous tissue disorders | 0 of 1 | 1 of 3 |
| Yawning | Respiratory, thoracic and mediastinal disorders | 0 of 1 | 1 of 3 |
| Lethargy | Nervous system disorders | 0 of 1 | 1 of 3 |
The safety counts distinguish serious adverse events from other adverse events and report both participants at risk and participants affected. In the lofexidine group, 0 of 1 participant at risk was recorded with a serious adverse event and 0 of 1 with another adverse event. In the placebo group, 0 of 3 participants at risk was recorded with a serious adverse event and 3 of 3 with another adverse event. Deaths were 0 in both groups.
These counts describe what the registry reports; they do not establish that treatment caused or prevented an event. The groups are very small, and the number at risk differs between them. A zero count in a small group does not rule out a possible event rate in a larger group. Likewise, the other-adverse-event count in the placebo group is a record of observed participants, not by itself a causal comparison.
The registry provides no serious-event terms and no additional event-level details, severity descriptions, onset information, or attribution assessments. The endpoint timeframe is Day 1 through Day 28, but the record does not provide enough detail to reconstruct event timing or determine how repeated events were handled. These safety figures are therefore best read as sparse descriptive observations.
12. What the Result Does, and Does Not, Mean
The registry record documents a randomized, quadruple-masked, placebo-controlled pilot study of lofexidine during an opioid taper, with enrollment of 4. It records a small number of safety observations across the two groups and identifies outcomes intended to cover safety, withdrawal symptoms, and taper progress. These details describe the study and the posted record; they do not establish an effect of treatment.
The available safety counts show no serious adverse events or deaths in either group, while other adverse events were recorded for all 3 participants at risk in the placebo group and none of the 1 participant at risk in the lofexidine group. Because the groups are so small, these observations cannot provide a precise estimate of comparative safety. The registry does not report a single comparative primary-outcome result, a confidence interval, or a statistical test.
The broader study question concerned reducing withdrawal symptoms and helping participants reduce opioid dose compared with placebo. The registry lists withdrawal scales and taper-related secondary outcomes, but the registry entries available for the trial do not include their results. No efficacy conclusion can be drawn from outcome names alone. The record also does not report why the trial was terminated or whether the enrollment and follow-up were complete.
General interpretation: A small pilot study can describe whether a trial process was undertaken and can provide preliminary observations, but the precision and generalizability of estimates depend on the amount and completeness of outcome data. Here, the available counts are too limited to settle the broader comparative questions. They should not be treated as proof of benefit, proof of no benefit, or proof that a treatment is free of risk.
13. Why This Trial Matters Statistically
This trial is statistically notable because its registry record combines a randomized, masked design with enrollment of only 4. Randomization and masking are important design features, but they cannot compensate for the limited information in a very small set of observations. The count for an individual participant can materially change the descriptive picture when group sizes are this small.
The distinction between an outcome being registered and an outcome having a reported result is important. The registry names a primary safety endpoint and several secondary measures relevant to withdrawal and taper progress, yet it lists 0 analyses and does not provide a single comparative primary-outcome estimate. Readers therefore need to separate the study’s stated questions from what the posted results can answer.
The record also illustrates why safety counts need denominators and context. The number of participants at risk differs between the two arms, and raw counts do not quantify the precision of a treatment contrast. Without a reported analysis method, confidence interval, and complete description of outcome data, the counts remain descriptive rather than a stable estimate for broader populations.
Finally, the terminated status matters as a feature of the record, but its significance is unclear because the reason is not reported. Statistical interpretation depends not only on design labels and observed counts, but also on knowing what was planned, what data were collected, and how incomplete observations were treated. Those details are not reported in the registry record, limiting the conclusions available from this study.
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.
Enrollment was 4, with 1 participant at risk in the lofexidine group and 3 in the placebo group for the reported safety counts. This leaves very little information for estimating how frequently adverse events occur or for comparing the groups precisely. The observed counts are sensitive to individual participants and cannot support broad conclusions about treatment differences.
The registry status is terminated, but the reason for termination is not reported in the registry record. It also does not report a planned enrollment target, whether recruitment ended as intended, participant completion, or the completeness of outcome collection. These unknowns make it difficult to judge how the available observations relate to the study’s original aims.
The primary outcome is named, but no single comparative result, confidence interval, or statistical test is reported. The record lists 24 outcome measures and 0 analyses. Arm descriptions are blank, and the record does not report dosing, detailed taper procedures, eligibility criteria, or the analysis population. Methods for handling missing data and multiple outcomes are also not reported.
Although secondary measures address withdrawal and taper outcomes, their results are not included in the registry record for this trial. The safety information does not include serious-event terms, event-level details, or assessments of whether events were related to treatment. These limitations mean that the record supports only a narrow descriptive account and does not settle the comparative safety or efficacy questions stated in the study description.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Randomized, Double-Blind, Placebo-Controlled Pilot Study on the Safety and Effectiveness of LUCEMYRA During an Opioid Taper in Treatment of Withdrawal — NCT04070157.
- Registry record last updated 2024-10-21; status last verified 2024-10.
- Results first posted 2024-10-21.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
This Phase 2 study, NCT04070157, was a randomized, quadruple-masked, parallel-group pilot comparing lofexidine with placebo during an opioid taper in subjects with chronic non-cancer pain. The sponsor was USWM, LLC (dba US WorldMeds). The registry reports a start date of 2019-08-02, a primary completion date of 2019-11-27, terminated status, and enrollment of 4.
The primary endpoint was the number of participants with treatment-emergent adverse events and serious adverse events from Day 1 through Day 28. The safety record reports no serious adverse events or deaths in either arm, and other adverse events among 0 of 1 participant at risk in the lofexidine group and 3 of 3 in the placebo group. The registry lists 24 outcome measures and 0 analyses. A single comparative primary-outcome result, the reason for termination, and detailed analysis methods are not reported in the registry record.