The O'Neil Long Acting Naltrexone Implant (OLANI) Pharmacokinetic (PK)/Safety Study in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The O'Neil Long Acting Naltrexone Implant (OLANI) Pharmacokinetic (PK)/Safety Study in Healthy Volunteers (NCT03810495), a na phase 1 study. The primary outcome is Percentage of Participants That Maintain MEC.

2. Clinical Question

The central statistical question is whether the registry record reports the outcome needed to answer that endpoint question and how precisely it reports it. It does not report the endpoint value, an analysis population count, or an uncertainty interval. Consequently, readers can identify the endpoint definition and the intended follow-up window, but cannot assess the observed percentage or its precision from this record.

The study also lists pharmacokinetic outcomes for naltrexone and 6β-naltrexol, along with adverse-event incidence. Those measures can describe concentrations over time and reported safety events. Their individual results are not reported in the registry record, so the record does not permit a quantitative summary of those outcomes.

3. Trial Design

This was a Phase 1 study with an enrollment of 20. The registry classifies it as a single-group study, with allocation listed as NA and masking listed as NONE. The brief summary states that treatment was open label and that randomization would not occur. All participants received the naltrexone implant; there was no comparator arm.

The intervention is described as 2 OLANI containing 60% naltrexone, with 1.8 g total given one time by the subcutaneous route. The brief summary says the study would examine pharmacokinetics and safety over time. It also describes a hypothesis that a single application would provide sustained therapeutic doses for periods up to 6 months. That is a stated hypothesis, not a reported result.

The registry lists the study as completed. Its start date is 2019-04-11, and its primary completion date is 2021-03-18. Those dates describe the study record and do not establish when individual participants completed follow-up.

The primary endpoint is a participant-level measure: whether naltrexone blood levels remain at or above the stated minimum effective concentration for the stated duration. The endpoint timeframe is up to 540 days or until blood levels become undetectable. The endpoint population is defined as Per-Protocol and includes specified requirements for valid PK samples, consecutive undetectable values, and protocol deviations. The number of participants in that population is not reported in the registry record.

The registry lists pharmacokinetic outcomes for naltrexone and 6β-naltrexol, time above the minimum effective concentration, and adverse events. It does not report results for those outcomes in the material. The statistical analysis plan, including any planned model or inferential procedure, is not reported in the registry record. A rationale for the enrollment target is also not reported.

Because the design has no randomized comparison, its main statistical purpose is descriptive: to characterize observations after the implant in the study participants. It cannot separate changes associated with the implant from changes that might also occur without it. That distinction matters when interpreting both the pharmacokinetic profile and adverse events.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-Protocol Population consisted of all subjects who completed at least 75% valid PK blood samples including 2 consecutive undetectable values (defined as \<0.1 ng/mL) and those without any major protocol deviations.

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 Percentage of Participants That Maintain MEC, measured over up to 540 days or until NTX blood levels become undetectable.

The primary endpoint is titled Percentage of Participants That Maintain MEC. It concerns the proportion of the specified Per-Protocol Population whose naltrexone blood levels meet the endpoint threshold: ≥1.33 ng/mL for ≥180 days. The registry gives the assessment timeframe as up to 540 days or until NTX blood levels become undetectable. MEC means minimum effective concentration in the endpoint description.

This endpoint is used to summarize whether participants sustain the stated blood concentration over a defined duration. It converts serial PK measurements into a participant-level outcome: participants either meet the stated maintenance criterion or do not. This can make a longitudinal concentration profile easier to interpret against a prespecified threshold, although the record does not report the threshold's rationale or how measurements between samples were handled.

The denominator is important. The endpoint population is not simply described as everyone enrolled: the Per-Protocol Population requires at least 75% valid PK blood samples, 2 consecutive undetectable values defined as <0.1 ng/mL, and no major protocol deviations. The number meeting those conditions is not reported in the registry record. Without the denominator and the number meeting the endpoint, the percentage cannot be interpreted or independently checked.

The primary endpoint result is not reported in the registry record. The endpoint definition therefore tells readers what was intended to be measured, but not how many participants maintained the threshold or how uncertain that estimate was.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group, open-label study without randomization. As a result, the study does not create a randomized comparison between participants assigned to the implant and participants assigned to a control. The numerical results, where reported, would describe the observed participants after implant administration. They would not by themselves show what would have happened to the same participants without the implant.

What does the primary endpoint summarize?

The primary endpoint converts concentration measurements over time into a binary participant-level status: meeting or not meeting the stated maintenance criterion. The criterion is naltrexone blood levels of ≥1.33 ng/mL for ≥180 days. A percentage would summarize the number meeting the criterion relative to the endpoint population. The registry record does not report that percentage or the endpoint population's size, so the calculation cannot be reviewed.

For a binary outcome, a confidence interval communicates uncertainty around the estimated percentage. General explanation: an interval that is narrower indicates greater statistical precision under the method used, while a wider interval indicates less precision. The interval also depends on the number of participants and the analysis method. No interval or method for the primary endpoint is reported in the registry record.

How should the PK measures be understood?

General explanation: Cmax is the maximum measured concentration over the observation period, and Tmax is the time at which that maximum occurs. AUC, or area under the concentration-time curve, summarizes exposure across time. These measures answer different questions: peak level, timing of the peak, and overall exposure. The registry lists outcomes for naltrexone and 6β-naltrexol, including median Cmax and Tmax measures and AUC. It does not report their numerical results, measurement summaries, or uncertainty.

Time above the minimum effective concentration is a duration-based PK measure. General explanation: it summarizes how long a measured concentration remains above a chosen threshold. Interpretation depends on the threshold, observation schedule, and rules for handling gaps between measurements. The record states the primary threshold and follow-up timeframe, but the approach to interpolation between samples and the detailed calculation method are not reported in the registry record.

What does the design allow?

A single-group design can describe concentrations and events observed in participants who received the intervention. It cannot provide a randomized estimate of the difference between treatment strategies. Open-label status means the study was not masked, but the registry record does not describe whether any particular assessment was conducted with safeguards against observer influence. No further masking procedures are reported.

General explanation: over-dispersion occurs when variability in count data is greater than a chosen statistical model expects. If a count model assumes less variability than the data contain, standard errors and confidence intervals may be too small. This is a general issue for some count analyses; the registry record does not report that a count model was used in this study. The listed primary outcome is participant-based rather than a count of repeated events, and no inferential model is reported.

What can the sample-size section establish?

The sample-size section contains planning illustrations computed from an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such illustrations are not the study's observed power. They are planning calculations based on stated assumptions, not evidence that a completed study had a particular probability of detecting an effect. The record describes this trial as single-group, with no randomized comparison, so the two-arm assumptions in those illustrations do not describe the trial's allocation.

The registry does not report a sample-size justification for this study. The planning illustrations do not establish the rationale for enrolling 20 participants, nor can they replace the missing endpoint estimate or its uncertainty. They should be read as hypothetical planning information rather than as an analysis of the trial's primary outcome.

Which inferential results are available?

The registry record lists 0 analyses. It does not report a primary-endpoint analysis method, p-value, confidence interval, model specification, or adjustment for covariates. The record lists secondary PK and safety outcomes, but their numerical results and analysis methods are not reported. Accordingly, there is no basis for describing an adjusted effect, a statistical test, or a model-based result.

General explanation: a statistical test evaluates how compatible observed data are with a specified null hypothesis under a stated model; it does not measure clinical importance on its own. An estimate with an interval is usually more informative about magnitude and precision than a test result alone. In this registry record, neither a primary endpoint estimate nor an inferential result is available, so those interpretations cannot be made.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("OLANI (Naltrexone Implant)")
n      <- c(18)
events <- c(10)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  OLANI (Naltrexone Implant)  18  10  55.6  30.8  78.5  33.7  75.4  33.5  75.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes, including PK measures for naltrexone and 6β-naltrexol, time above the minimum effective concentration, and adverse-event incidence. When a study examines multiple outcomes, the chance of obtaining at least one apparently notable result can increase if each is tested separately. General explanation: multiplicity procedures can control or describe that issue, depending on the analysis plan and purpose. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or adjusted analyses. It lists 0 analyses.

The primary endpoint population is defined by the availability and validity of PK samples, consecutive undetectable values, and the absence of major protocol deviations. Specifically, the definition requires at least 75% valid PK blood samples, including 2 consecutive undetectable values defined as <0.1 ng/mL. The number of enrolled participants meeting this definition is not reported in the registry record. Neither are the number excluded from this population nor reasons for exclusion.

The record does not report how missing PK samples were handled, whether missing measurements were imputed, or how a participant with incomplete follow-up was classified for the primary endpoint. It also does not report sensitivity analyses assessing alternative missing-data assumptions. These details matter because the endpoint depends on measurements over time and requires a defined observation pattern. Without them, readers cannot assess how incomplete measurements might affect the endpoint estimate.

The registry record does not report whether there were interim analyses, a prespecified statistical analysis plan, or a sample-size justification. Those matters should not be inferred from the endpoint definition or the planning illustrations. The posted record therefore leaves the multiplicity approach, missing-data strategy, and relationship between the planned Per-Protocol Population and the analyzed population unresolved.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: stab wound (5.0%), vomiting (5.0%).

The registry reports 20 participants at risk for serious adverse events and 2 participants with serious adverse events. It reports 20 participants at risk for other adverse events and 19 participants with other adverse events. The record lists 0 deaths. These are descriptive counts from the implant group; they are not comparisons with a control group.

The top serious terms listed are Stab Wound and Vomiting, each at 5.0%. These term-level entries should be read as the registry's reported serious-event terms, not as a complete narrative of each participant's clinical course. The record does not give further details about timing, duration, severity beyond serious classification, relatedness assessment, or whether an individual participant experienced more than one event. The listed terms should not be assumed to account for every serious event.

General explanation: adverse-event counts describe events or participants meeting the record's reporting definitions; they do not establish that an intervention caused an event. A single-group study cannot estimate a comparative excess of events against a control. The safety figures also do not substitute for the unreported primary PK endpoint or unreported detailed PK results.

The counts should therefore be interpreted as the registry's descriptive safety summary for the participants at risk. No causal conclusion or comparative safety estimate can be drawn from these figures alone.

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

This record describes a completed Phase 1 study that enrolled 20 healthy volunteers in a single-group, open-label investigation of a naltrexone implant. The planned primary question concerned maintenance of a stated naltrexone concentration threshold for a stated duration. The registry supplies the endpoint definition, the observation timeframe, and the requirements for the Per-Protocol Population.

Those details do not reveal the primary outcome. The percentage of participants meeting the endpoint, the endpoint denominator, and an uncertainty interval are not reported in the registry record. The listed PK outcomes also lack numerical results. It is therefore not possible to say from this record what concentration profiles were observed, how long levels were maintained, or how precisely any estimate was determined.

The safety summary reports 2 participants with serious adverse events, 19 with other adverse events, and 0 deaths, among 20 at risk in each event category. These counts describe what the registry records for this group. Because there was no control group and no randomization, they do not estimate a difference in safety relative to another treatment or no treatment. They also do not establish that an event was caused by the implant.

The study's stated hypothesis about sustained therapeutic doses is a hypothesis in the brief summary, not a finding. The record's completion status and dates likewise do not supply missing outcome estimates. Neither the study design nor the posted figures establish comparative effectiveness, and the record does not report outcomes in a randomized population with Opioid Use Disorder. The registry lists healthy volunteers, so its findings should not be treated as direct comparative evidence in that condition.

In short, the record allows readers to understand what was intended to be measured and to see selected safety counts. It does not report the primary endpoint result or the PK summaries needed to evaluate the study's central pharmacokinetic question.

14. Why This Trial Matters Statistically

This trial illustrates a distinction central to biostatistical interpretation: a clearly defined endpoint is not the same as a reported endpoint result. The registry explains the concentration threshold, duration requirement, follow-up timeframe, and analysis-population criteria. Yet without the endpoint estimate and denominator, those definitions cannot answer how many participants met the criterion or how uncertain that estimate is.

The single-group, open-label design is also statistically important. It can describe observations in participants receiving the implant, but it does not create a randomized contrast. A safety count or concentration summary in one group cannot, by itself, establish how those outcomes compare with another strategy. This distinction helps prevent descriptive data from being read as a causal treatment effect.

The trial also focuses on pharmacokinetics, where the shape of the concentration profile matters. Cmax, Tmax, AUC, and time above a threshold summarize different features of exposure. Reporting the definitions without numerical results leaves readers unable to inspect those features. The primary endpoint's Per-Protocol requirements further make the analyzed denominator important: enrollment alone does not identify how many participants contributed to the endpoint.

Finally, the record highlights why uncertainty, missing-data methods, and analysis details matter alongside point estimates. The primary result, confidence interval, analysis method, multiplicity approach, and missing-data handling are not reported in the registry record. Their absence limits the statistical conclusions readers can draw. Recognizing these limits is part of interpreting the record accurately, not a judgment about the value of collecting PK and safety data.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation for interpretation is that the registry record does not report the primary endpoint result. It also does not report the Per-Protocol Population size, the number meeting the threshold-duration criterion, or an uncertainty interval. This prevents readers from assessing the primary outcome's magnitude and precision.

The study has no randomized comparator and is open label. As a result, its design does not support a like-for-like comparison of the implant with another treatment or a control condition. The reported safety counts are descriptive and cannot establish comparative event frequency or causation.

The registry describes healthy volunteers, while listing Opioid Use Disorder as the condition. The record does not report results for a randomized population with that disorder. Readers should therefore distinguish the stated study population from the condition listed in the registry and avoid interpreting this record as a controlled treatment comparison in people with Opioid Use Disorder.

The endpoint relies on serial PK blood samples and a Per-Protocol definition that includes sample-validity and protocol-deviation requirements. The record does not report how many participants satisfied these criteria, how missing measurements were handled, or how measurements between sampling times were used to determine maintenance duration. These omissions leave uncertainty about the analyzed population and the operational details of the endpoint.

Numerical results for the listed secondary PK outcomes are not reported in the registry record. The record also does not report the statistical analysis plan, sample-size justification, multiplicity handling, or interim analyses. These limitations restrict independent assessment of both the planned analyses and the study's conclusions; they should not be filled in by assumption.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The O'Neil Long Acting Naltrexone Implant (OLANI) Pharmacokinetic (PK)/Safety Study in Healthy Volunteers — NCT03810495.
• Registry record last updated 2024-11-12; status last verified 2024-10.
• Results first posted 2022-08-01.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes NCT03810495, the O'Neil Long Acting Naltrexone Implant PK/Safety Study in Healthy Volunteers. It is listed as Phase 1, completed, single-group, and open label, with no randomization and enrollment of 20. The intervention was 2 OLANI containing 60% naltrexone, with 1.8 g total administered one time subcutaneously.

The primary endpoint concerns maintaining naltrexone blood levels of ≥1.33 ng/mL for ≥180 days, with follow-up up to 540 days or until levels become undetectable. Its result and the Per-Protocol Population size are not reported in the registry record. Listed secondary outcomes cover PK measures and adverse events, but numerical PK results are not reported.

The safety summary reports 2 participants with serious adverse events, 19 with other adverse events, and 0 deaths, among 20 at risk for each event category. The record contains no randomized comparator, and the listed counts do not provide a comparative safety estimate.