Evaluation of Safety of Repeated Doses of OP0201 Metered Dose Inhaler Compared to Placebo in Healthy Adult Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Safety of Repeated Doses of OP0201 Metered Dose Inhaler Compared to Placebo in Healthy Adult Volunteers (NCT03748758), a randomized phase 1 study. The primary outcome is Number of Participants With of Adverse Events.

2. Clinical Question

The central statistical question is therefore how to interpret participant counts from a small, early-phase study with two OP0201 dose groups and a placebo group. The study was randomized, quadruple masked, and parallel, but the registry record does not report the randomization ratio or explain which roles were masked. It also does not provide a definition of an adverse event or state whether the primary count includes events regardless of whether they were considered related to treatment. Those details matter when comparing event counts across groups.

The posted results also include counts of participants with serious adverse events and deaths. They list zero serious adverse events and zero deaths in each group. These outcomes address different questions from the primary count of participants with adverse events overall; the counts should not be treated as interchangeable.

3. Trial Design

This was a completed Phase 1, randomized, quadruple-masked, parallel-group study sponsored by Novus Therapeutics, Inc. The registry record lists a start date of 2018-11-27 and a primary completion date of 2019-03-20. Its stated purpose was to evaluate safety and tolerability of two dose levels of OP0201 and placebo when administered intranasally to healthy adults.

The trial had two OP0201 regimens. Cohort A received 30 mg per day for 14 days, while Cohort B received 60 mg per day for 14 days. The placebo descriptions specify 0 mg per day for 14 days in each cohort. In the posted primary-outcome results, the 30 mg per day group has 12 participants, the 60 mg per day group has 12 participants, and the placebo group has 6 participants. These are group counts as listed in the registry record; the record does not state the intended allocation ratio.

Randomization can help make treatment groups comparable on average, while masking can reduce the influence of expectations on care and outcome assessment. Those are general design principles; the registry record does not describe the randomization method, allocation concealment, the specific people masked, or how masking was maintained. The parallel model indicates that participants were assigned to a study group rather than described as crossing through multiple treatment regimens. Further details about visit schedules, dose escalation, and cohort sequencing are not reported in the registry record.

The primary outcome timeframe is 21 Days, while each regimen description specifies 14 days of dosing. The record does not explain the timing of outcome assessments in relation to dosing, or provide a more detailed follow-up schedule. It lists four secondary outcomes concerning systemic exposure: observed and baseline-corrected serum concentrations for DPPC and CP at nominal timepoints. Numerical outcome results for those measures are not included in the posted results described in the registry record.

The study is marked completed. Completion status does not by itself establish that every planned analysis or outcome was reported. The record lists five outcome measures and zero analyses. A formal protocol, statistical analysis plan, and additional details about the study conduct are not reported in the registry record.

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

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 Number of Participants With of Adverse Events, measured over 21 Days.

The primary endpoint is recorded as the number of participants with adverse events, with participants as the unit and a 21 Days timeframe. This is a binary participant-level outcome: a participant either contributes to the count as having an adverse event or does not. The posted values are counts of participants affected, not counts of every individual event. A participant who experienced more than one event would still be represented as one participant in this endpoint, according to its stated count-of-participants form.

In safety studies, counting participants with adverse events offers a direct summary of how many people experienced an event during the stated observation period. It can be useful alongside details about event types, seriousness, timing, and attribution. The registry record does not provide an adverse-event definition, event-level descriptions for the primary outcome, severity classifications for non-serious events, or a statement about whether investigators judged events to be treatment-related. The primary count alone therefore cannot describe the full pattern or clinical importance of events.

The reported counts are 5 participants for OP0201 30 mg per day, 9 for OP0201 60 mg per day, and 4 for placebo. The corresponding group sizes are 12, 12, and 6 participants. No uncertainty interval or inferential test for the primary outcome is posted in the registry record. Without such information, the counts should be read descriptively rather than as precise estimates of the underlying event probabilities or as evidence of a statistically established difference.

The endpoint is appropriate to a safety and tolerability question, but it does not directly measure systemic exposure, symptom benefit, or any other clinical outcome. Exposure is addressed in the listed secondary outcomes, which concern serum concentrations of DPPC and CP. Numerical results for those outcomes are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary at the participant level: it counts participants with an adverse event. General statistical explanation: binary outcomes are often described by the number of participants with the event and the number assessed in each group. A comparison can then be expressed using a measure such as a risk difference, risk ratio, or odds ratio. Each measure answers a slightly different question, and each requires a clearly specified analysis population and handling of missing outcomes. The registry record posts group counts and group sizes but does not report a treatment-effect estimate for this endpoint.

What do the event counts convey?

The counts convey how many participants were recorded as affected in each group during the stated timeframe. They do not convey the number of event episodes. For example, a participant with more than one event remains one participant in a count-of-participants outcome. This distinction matters because an event-based analysis could give a different summary if some participants experienced repeated events. The registry record does not post event-level data or say whether repeated events were analyzed separately.

For the 30 mg per day group, the posted count is 5 participants with adverse events among 12 participants; for the 60 mg per day group, it is 9 among 12; and for placebo, it is 4 among 6. These are the directly reported group counts and denominators. No additional arithmetic is needed to interpret them as counts. The registry record does not report a confidence interval or statistical test for the group contrasts.

Why does uncertainty matter?

General statistical explanation: an estimate from a sample is uncertain because the observed participants are only one possible set of outcomes under the study conditions. A confidence interval is a range of values generated by a statistical procedure to reflect uncertainty about an underlying quantity, under the assumptions of that procedure. It does not guarantee that the true value lies within the interval, and it is not a measure of clinical importance. For a binary outcome, interval estimates can be especially wide when groups are small or event counts are sparse. The registry record does not report confidence intervals for the primary endpoint, so the precision of the group comparisons cannot be assessed from posted inferential statistics.

Different measures of effect can also communicate different aspects of a comparison. A risk difference describes an absolute contrast in event probabilities, while a ratio measure describes a relative contrast. Neither should be calculated from these counts in this explanation, and the record does not select or report an effect measure. A statistical comparison would also require a method appropriate to the design and data, and the registry record does not report that method.

What is the status of the two-arm comparison?

The record indicates that values are missing or not estimable for a two-arm comparison of the binary endpoint. It lists zero analyses. As a result, there are no posted pairwise estimates, confidence intervals, or p-values to describe. The sponsor's own analysis would take precedence if a discrepancy between that analysis and a recalculation were identified; the record does not indicate such a discrepancy. No recalculated comparison is reported.

General statistical explanation: in a randomized trial, a statistical comparison usually targets an effect of assignment to a group, but its interpretation depends on the analysis population and missing-data rules. An intention-to-treat analysis, for example, is defined by including participants according to randomized assignment, while other populations may use different inclusion criteria. The registry record does not report which analysis population was used for the primary endpoint, whether all randomized participants were assessed, or how missing observations were handled.

How should planning calculations be understood?

Any planning illustration based on an observed effect is hypothetical rather than a description of the trial's original design. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set as a stated fraction of the observed effect. Such illustrations estimate participants per arm for 80% power under their assumptions; they are not observed power and do not show the probability that the trial's result is correct. The registry record does not report a sample-size justification for the trial or establish that those planning assumptions were used when the study was designed.

General statistical explanation: over-dispersion is relevant when observed variability exceeds what a model assumes. It can make standard errors too small if ignored, leading to intervals that are too narrow or tests that are too liberal. This is more directly relevant to outcomes with counts of repeated events than to a participant-level binary outcome. The primary endpoint counts participants with adverse events, not the total number of event episodes; the registry record provides no event-level distribution from which to assess over-dispersion.

What can be said about the secondary outcomes?

The registry record lists four systemic-exposure outcomes based on DPPC and CP serum concentrations: observed concentrations and baseline-corrected concentrations by nominal timepoint. Their units are µg/mL for DPPC and µM for CP. The actual concentration values, timepoint-specific analyses, uncertainty estimates, and analysis methods are not reported in the registry record. Thus those outcomes cannot add a numerical exposure comparison to the interpretation of the primary endpoint.

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("Drug: OP0201 Cohort A 30 mg Per Day", "Drug: OP0201 Cohort B 60 mg Per Day", "Drug: Placebo")
n      <- c(12, 12, 6)
events <- c(5, 9, 4)
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  Drug: OP0201 Cohort A 30 mg Per Day  12  5  41.7  15.2  72.3  19.3  68.0  19.2  68.4
ARM  Drug: OP0201 Cohort B 60 mg Per Day  12  9  75.0  42.8  94.5  46.8  91.1  46.2  90.9
ARM  Drug: Placebo  6  4  66.7  22.3  95.7  30.0  90.3  29.0  90.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists four secondary outcomes in addition to the primary adverse-event outcome. The secondary outcomes concern observed and baseline-corrected serum concentrations of DPPC and CP by nominal timepoint. No secondary-outcome results or analysis details are reported in the registry record. The record lists five outcome measures and zero analyses.

Multiplicity arises when several outcomes, timepoints, or group comparisons are tested. General statistical explanation: as the number of statistical tests increases, the chance of at least one nominally unusual result can increase if no adjustment or prespecified hierarchy is used. Methods such as adjustment of significance thresholds or hierarchical testing can address this issue, but the appropriate approach depends on the scientific aims and analysis plan. Whether any multiplicity adjustment was planned or performed is not reported in the registry record.

The registry record does not report a statistical analysis plan, prespecified hierarchy among outcomes, or a list of planned comparisons. It also does not say whether the primary outcome was analyzed for all randomized participants or for a different analysis population. The record does not describe how participants with missing outcome data were treated, whether any data were imputed, or whether missingness differed across groups. These omissions limit the ability to assess possible bias in the posted counts or to reproduce an analysis.

Randomized assignment is recorded, but the record does not provide details about allocation concealment, deviations from assigned treatment, adherence, withdrawals, or the number of participants assessed at each outcome timepoint. The group sizes in the posted primary results should not be assumed to define every analysis population. Without these details, it is not possible to determine from the registry record whether the posted endpoint counts include every randomized participant or how incomplete follow-up was handled.

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 non-serious adverse event terms

The serious adverse event entries are zero in the OP0201 30 mg per day group, zero in the OP0201 60 mg per day group, and zero in the placebo group. The death entries are also zero in each group. These are the figures posted in the registry record for serious adverse events and deaths.

They should be read separately from the primary outcome, which counts participants with adverse events of any stated seriousness and lists 5 participants in the 30 mg per day group, 9 in the 60 mg per day group, and 4 in the placebo group. The registry record does not provide a definition of seriousness, event-level descriptions, or details about causality assessments. It does not state whether events were judged related to study treatment.

A zero count in a group means that no event of that type was reported for that group in the posted results. General statistical explanation: zero observed events do not establish zero underlying risk. The amount of uncertainty depends on factors such as the number of participants observed, follow-up duration, and the completeness of event ascertainment. The record does not provide an uncertainty interval for serious adverse events or additional follow-up information. These entries therefore describe the recorded study experience, rather than ruling out the possibility of serious events in other participants or settings.

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

The posted results establish a descriptive record of adverse-event participant counts for three groups in a randomized Phase 1 study of healthy adult volunteers. The counts are 5 participants for OP0201 30 mg per day, 9 for OP0201 60 mg per day, and 4 for placebo. Serious adverse events and deaths are each recorded as zero in all groups. These are the results that can be stated from the registry record without adding an unreported statistical analysis.

The results do not establish a treatment effect. There is no posted estimate of a difference between OP0201 and placebo, no confidence interval, and no p-value for the primary outcome. The record also does not provide an analysis method, missing-data handling, or a complete description of event types and attribution. Without these elements, the numerical counts cannot determine whether apparent variation between groups is more than random variation, or whether events were caused by treatment.

Nor do the data establish that the treatment is safe or unsafe in a broader population. The study concerns healthy adult volunteers and reports group sizes of 12, 12, and 6 participants for the primary endpoint. The dosing descriptions specify 14 days, and the endpoint timeframe is 21 Days. The registry record does not provide longer follow-up. Findings from this setting and observation period cannot by themselves characterize uncommon events, longer-term safety, or outcomes in people with conditions not represented in the study.

The listed systemic-exposure outcomes do not change that interpretation because their numerical results are not reported in the registry record. In addition, the record does not describe a clinical benefit endpoint. Safety counts and serum exposure measurements address different questions; neither alone establishes whether a treatment has clinical benefit.

Accordingly, the appropriate reading is narrow and descriptive. The registry record documents participants with adverse events and reports no serious adverse events or deaths in the posted group results. It does not provide the inferential or contextual information needed to attribute events, rank the dose groups, or make a general conclusion about treatment effects. These results are not medical advice.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a safety-focused early-phase study can yield descriptive data without a reported inferential comparison. Its randomized, quadruple-masked, parallel design is relevant to how treatment groups were organized, while its small group sizes and participant-level event counts frame how much can be concluded from the posted results. The design features do not replace a reported analysis or make the counts precise on their own.

The endpoint also illustrates the difference between counting participants with an event and counting event episodes. A participant-level count offers a straightforward summary of how many people experienced an adverse event, but it does not describe recurrent events or their distribution by type and seriousness. Event-level data and definitions would be needed to answer those other safety questions. The registry record contains separate serious-event counts, but does not provide a detailed event description.

The record's lack of a posted statistical comparison is important for interpretation. Readers can identify the observed counts and group sizes, but cannot assess an estimated contrast and its uncertainty from the registry information. This distinction is central to clinical trial reading: descriptive differences are not equivalent to evidence that groups differ beyond what sampling variability could plausibly produce.

The study also highlights the limits of registry summaries. Four systemic-exposure outcomes are listed, yet numerical results are not reported in the record. The analysis populations, missing-data approach, and multiplicity strategy are also not reported. These details affect reproducibility and the interpretation of a set of outcomes, especially when several outcome measures or timepoints are of interest.

For biostatisticians and clinical researchers, the record emphasizes the value of reporting prespecified methods, effect estimates with uncertainty, participant flow, and outcome definitions alongside group counts. Those details support transparent evaluation of both the results and their limitations. The available information remains useful as a description of the registered study and its posted adverse-event counts, but it cannot answer questions that require unreported analyses or outcome 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 primary limitation is that the registry record does not post an inferential analysis for the binary adverse-event endpoint. It lists participant counts and group sizes, but no treatment-effect estimate, confidence interval, or p-value. Values are noted as missing or not estimable for a two-arm comparison, and the record lists zero analyses. Consequently, the precision of comparisons and compatibility of group differences with chance cannot be evaluated from the record.

Important endpoint details are also absent. The record does not define adverse events, explain how seriousness or treatment relatedness was judged, or provide event-level descriptions. The primary outcome counts participants affected rather than separate events, so information about repeat events is not available. Serious adverse event and death counts are posted, but further details about ascertainment and follow-up are not reported.

The registry record does not describe the primary analysis population, missing-data rules, participant withdrawals, adherence, or the number assessed at each timepoint. It also does not provide a statistical analysis plan, multiplicity approach, allocation method, masking procedures, or a sample-size justification. Without these details, the reproducibility of the analysis and the risk of bias from incomplete observation cannot be fully assessed.

Generalizability is limited by the stated population of healthy adult volunteers, the early-phase study setting, and the reported group sizes. The endpoint timeframe is 21 Days, and the regimen descriptions specify 14 days of dosing; longer-term outcomes are not reported. The listed systemic-exposure outcomes lack numerical results in the registry record. These limitations leave the posted information focused on short-term descriptive safety counts rather than a comprehensive assessment of safety or clinical effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Safety of Repeated Doses of OP0201 Metered Dose Inhaler Compared to Placebo in Healthy Adult Volunteers — NCT03748758.
• Registry record last updated 2020-02-25; status last verified 2020-02.
• Results first posted 2020-02-25.
• 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 record describes a completed, randomized, quadruple-masked, parallel Phase 1 study sponsored by Novus Therapeutics, Inc. It enrolled healthy adult volunteers and evaluated intranasal OP0201 at 30 mg per day and 60 mg per day for 14 days, with placebo groups described for Cohort A and Cohort B.

The primary outcome is the number of participants with adverse events during 21 Days. Posted counts are 5 participants in the 30 mg per day group, 9 in the 60 mg per day group, and 4 in the placebo group. The record lists zero serious adverse events and zero deaths in each group. It does not post an inferential comparison for the primary outcome.

Four secondary outcomes concerning observed and baseline-corrected DPPC and CP serum concentrations are listed, but numerical results are not reported in the registry record. The record lists five outcome measures and zero analyses. Details about analysis populations, missing data, multiplicity, and the statistical analysis plan are not reported.