Pharmacokinetic Study of OPC-1085EL Ophthalmic Solution in Healthy Male Adult Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic Study of OPC-1085EL Ophthalmic Solution in Healthy Male Adult Volunteers (NCT02108288), a randomized phase 1 study. The primary outcome is Cmax of Carteolol.

2. Clinical Question

In statistical terms, the study asks a pharmacokinetic question: how the blood concentration of carteolol is characterized over the stated treatment period under the listed ophthalmic regimens. Cmax describes the highest measured concentration during the relevant sampling period. The record also names Tmax of carteolol and Tmax of latanoprost acid as secondary outcomes. Tmax is the time at which the maximum concentration is reached, but the registry record does not give results for either secondary outcome.

The study is not described as a clinical efficacy trial measuring change in glaucoma or ocular hypertension. Its stated emphasis is on blood concentrations, and its population is identified as healthy male adult volunteers. The registry record does not specify a primary formal contrast among the three regimens, nor does it provide a hypothesis about the direction or size of a difference. Therefore, the study question can be described from the listed outcomes and regimen descriptions, but a claim about comparative pharmacokinetic effects cannot be made from the reported information.

3. Trial Design

The registry describes a randomized, unmasked, parallel-group Phase 1 study with enrollment of 30. Participants were assigned to one of three listed ophthalmic regimens: OPC-1085EL ophthalmic solution, carteolol long-acting ophthalmic solution, or latanoprost ophthalmic solution. Each regimen is described as once daily. The brief summary states that treatment was administered for 7 days.

In a parallel design, each participant is assigned to a regimen rather than crossing through all listed regimens. Randomization is intended, in general, to make treatment groups comparable with respect to factors known and unknown at allocation. It does not guarantee that every group is identical, particularly in a study with limited enrollment. The record identifies the allocation as randomized but does not report the sequence-generation method, allocation concealment, stratification factors, or whether assignment was balanced in practice.

The study is listed as having no masking. In general, lack of masking means that treatment assignment is not concealed from participants, investigators, or both; the registry record does not specify which people knew assignments. Knowledge of assignment can affect behavior, assessments, or study conduct. For pharmacokinetic outcomes, the degree of concern depends on the sampling and laboratory procedures, which are not described in the registry record.

The primary outcome is Cmax of carteolol, expressed as a mean with standard deviation, with a timeframe of Day 1 and Day 7. The record lists four outcome measures and identifies Tmax of carteolol and Tmax of latanoprost acid as secondary outcomes. It reports 0 analyses. That means the registry record does not provide a statistical analysis result for the outcomes; it does not establish that no analyses were performed outside the record.

The trial is marked completed. Its start and primary completion are recorded as 2014-04 and 2014-05. The study is sponsored by Otsuka Pharmaceutical Co., Ltd. The protocol details, planned sample-size justification, recruitment flow, and analysis populations are not reported in the registry record. The listed enrollment and design therefore describe the study structure, but they do not by themselves establish how many participants contributed data to each pharmacokinetic outcome or how the study was planned statistically.

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 Cmax of Carteolol, measured over Day 1 and Day 7.

The primary endpoint is Cmax of carteolol, reported in ng/mL as a mean with standard deviation, with measurements identified for Day 1 and Day 7. Cmax is the maximum concentration observed during a specified sampling interval. In pharmacokinetic studies, it is used to characterize peak systemic exposure after administration. It can help describe whether the concentration profile differs across regimens or across the stated measurement days, provided the sampling schedule and analysis are appropriately defined.

The mean describes the central value of the measured concentrations in a group. The standard deviation describes how spread out individual measurements are around that mean. These are descriptive summaries; neither alone establishes whether a difference between groups is statistically distinguishable from sampling variation. A comparison also requires a defined estimand or contrast, an analysis method, and uncertainty information such as a confidence interval. The registry record does not report the Cmax means or standard deviations, the sampling times, or a comparative estimate.

The endpoint is pharmacokinetic rather than a direct measure of improvement in glaucoma or ocular hypertension. A concentration measure can describe drug exposure, but the registry record does not establish a relationship between a concentration result and a clinical benefit or harm. It also does not report the primary endpoint results for Day 1 or Day 7. Accordingly, the endpoint's role can be explained, but its observed pattern and precision cannot be evaluated from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Pharmacokinetic outcomes describe how a substance is present in the body over time. Cmax is the maximum measured concentration during a defined sampling period, while Tmax is the time at which that maximum occurs. The registry identifies Cmax of carteolol as the primary outcome and Tmax of carteolol and Tmax of latanoprost acid as secondary outcomes. It does not report sampling schedules, concentration profiles, or numerical outcome values. Without those details, the endpoints can be defined conceptually but cannot be independently interpreted in relation to the observed data.

What does a mean and standard deviation describe?

The primary outcome is specified as a mean with standard deviation. In general, the mean summarizes the center of a set of measurements, and the standard deviation describes how much individual measurements vary around that center. A mean is useful for comparing average concentrations, while the standard deviation helps convey variability among participants. These summaries do not show the full shape of a distribution. If concentrations are strongly skewed, for example, a mean and standard deviation may not describe the typical participant particularly well. Whether that issue applies cannot be assessed because the registry record does not report the underlying measurements or distribution.

A descriptive difference between group means, if reported, would not alone show how precisely that difference was estimated. A confidence interval is a range generated by a statistical procedure that conveys uncertainty around an estimate. Narrower intervals generally indicate greater precision, while wider intervals indicate more uncertainty. The registry record does not report confidence intervals for Cmax or any other outcome. No interpretation of statistical significance or precision is therefore possible for the primary endpoint.

What does randomization contribute?

In general, random allocation helps reduce systematic differences between groups at the time of assignment. This supports a fairer comparison than assigning treatment according to participant characteristics or investigator choice. Randomization does not ensure that groups are balanced on every characteristic, and it does not address problems arising after assignment, such as missing measurements or departures from the assigned regimen. The record says the trial was randomized but does not describe the randomization process, concealment, adherence, or participant flow.

The parallel model means participants were assigned to one listed regimen rather than receiving every regimen in sequence. This avoids some complications associated with comparing repeated treatment periods within the same participant, but it makes the comparison dependent on how similar the groups are. Randomization is the design feature intended to support that comparability. The registry record does not provide baseline characteristics or an analysis adjusted for any covariates.

What can be learned from the planned sample-size assumptions?

The record includes a general description of planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is expressed as a fraction of the observed effect. It also distinguishes the way sample size is expressed for time-to-event outcomes from other outcomes. These statements describe assumptions used for planning illustrations; they do not establish the trial's original design rationale or its own sample-size justification. Numerical planning results are not reported in the registry record.

Such illustrations are conditional: a required sample size depends on the chosen effect to detect, variability assumptions, significance level, allocation, and analysis approach. When an effect is taken from observed data, the illustration is not evidence that the trial had a particular probability of finding a result. It is not observed power. The record does not provide a trial-specific power calculation, assumptions about Cmax variability, or a target effect that was selected before the study.

Why does over-dispersion matter in general?

Over-dispersion occurs when variability in the data is greater than a statistical model assumes. When present and ignored, standard errors can be too small and confidence intervals can be too narrow, making results appear more precise than they are. This issue is commonly discussed for count outcomes; the primary outcome is continuous. The registry record does not state that an over-dispersion model was used or that over-dispersion was assessed. The concept is general and should not be read as a description of the trial's analysis.

What does the count of reported analyses mean?

The registry record reports 0 analyses. That is a statement about the analyses presented in the record, not a statement that investigators conducted no statistical work. No model, test, estimator, adjustment, or handling of repeated measurements is described. In particular, the record does not clarify whether Day 1 and Day 7 were analyzed separately, jointly, or as a change over time. It also does not give a formal comparison across the three regimens. Without an analysis description and outcome estimates, a reader cannot reproduce or assess the primary inferential result.

For these reasons, statistical methods can be discussed as general principles, but the posted information does not support attributing a specific model or inferential procedure to this trial. The reported endpoint definition and design do not substitute for the missing analysis details.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures, including Cmax of carteolol as the primary outcome and Tmax of carteolol and Tmax of latanoprost acid as secondary outcomes. It does not describe the fourth measure in the information available, identify all planned comparisons, or state whether multiplicity was addressed. Multiplicity arises when several outcomes, time points, or contrasts are tested; conducting many tests can increase the chance of a nominally positive result by chance. General approaches include defining a primary comparison in advance, adjusting significance thresholds, or interpreting secondary analyses as exploratory. Which, if any, approach applied is not reported in the registry record.

The primary outcome includes Day 1 and Day 7, but the record does not say whether both time points were primary tests, whether one was the principal time point, or how repeated measurements were handled. It also does not report a statistical analysis plan, planned contrasts among the three regimens, or a hierarchy for the outcomes. These omissions prevent assessment of how the reported outcomes, if analyzed, would relate to a prespecified testing strategy.

Missing-data methods and analysis populations are not reported in the registry record. The record does not state how many participants contributed Cmax or Tmax measurements, how unavailable samples were treated, or whether analyses followed an intention-to-treat, per-protocol, or other population definition. A registry enrollment count is not a substitute for an outcome-specific analysis population. These details matter because exclusions or missing measurements can affect both the estimated group summaries and their interpretation.

There is no reported account of protocol deviations, withdrawals, or reasons for missing data. Consequently, the available record does not allow assessment of whether missingness could be related to treatment assignment or measured concentration. This uncertainty should be kept separate from any claim about the pharmacokinetic outcomes, for which numerical results are not reported.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for each of the three groups. For OPC-1085EL ophthalmic solution, 0 serious adverse events were reported among 10 participants at risk. For carteolol long-acting ophthalmic solution, the corresponding figures are 0 and 10. For latanoprost ophthalmic solution, they are also 0 and 10. These are the recorded serious-event counts in the registry, not proof that no serious event could occur or that the regimens have equivalent safety.

The record separately reports other adverse events affecting 6 participants in the OPC-1085EL group, 4 in the carteolol long-acting group, and 8 in the latanoprost group; each group has 10 participants at risk. These counts are descriptive. The registry information does not provide event terms, severity, duration, attribution, or a statistical comparison for these other events. A count of participants affected is also distinct from a count of all event episodes, and the record does not clarify whether individuals could have experienced more than one event.

Deaths are not reported in the registry record. The safety figures should be interpreted in the context of a Phase 1 study in healthy male adult volunteers and should not be treated as a complete assessment of uncommon or longer-term harms. The record does not provide enough detail to compare safety statistically.

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

This record establishes that a randomized, unmasked, parallel Phase 1 study enrolled 30 healthy male adult volunteers and compared three listed ophthalmic regimens administered once daily. Its primary outcome was Cmax of carteolol, specified as a mean with standard deviation in ng/mL at Day 1 and Day 7. Those details explain the study's design and measurement focus.

The record does not report the primary outcome values, a treatment contrast, uncertainty intervals, or an inferential analysis. It therefore cannot establish whether carteolol concentrations differed among regimens, how large any difference was, or how precisely it was estimated. The lack of a reported result should not be interpreted as a null result. The record also does not report the values for the named Tmax outcomes.

The study's stated purpose concerns blood concentrations of carteolol and latanoprost in relation to OPC-1085EL. The listed intervention arms and outcome descriptions do not specify a formal primary comparison in enough detail to characterize a comparative estimate. No conclusion about exposure equivalence, superiority, or a dose-response pattern can be drawn from the posted information.

The adverse-event counts indicate that 0 serious adverse events were reported in each group, and that other adverse events were recorded in each group. These counts are not a substitute for event descriptions or a comparative safety analysis. They do not establish causality, and they do not demonstrate that the regimens have the same safety profile. Deaths are not reported in the registry record.

Finally, the population and outcomes limit the scope of interpretation. Healthy male adult volunteers and blood-concentration measures do not answer whether treatment changes glaucoma or ocular hypertension outcomes. The registry record contains no clinical efficacy endpoint result and no analysis linking concentration measures to a clinical outcome. The defensible conclusion is about what the study was designed to characterize and what is recorded, not about clinical benefit or harm.

13. Why This Trial Matters Statistically

This study illustrates why pharmacokinetic endpoints and clinical outcomes need to be kept distinct. Cmax and Tmax describe concentration and timing, respectively. They can be important for characterizing exposure, but they are not themselves measures of a patient's clinical response. In this record, the primary endpoint is clearly identified, yet its numerical results are not reported. That gap makes the distinction especially important: knowing which outcome was planned is not the same as knowing what it showed.

The trial also highlights the role of an explicit comparison. Randomized allocation supports comparisons between assigned groups in general, but readers still need to know which contrast was prespecified and how it was analyzed. With three listed regimens and measurements at Day 1 and Day 7, the record would need to identify the intended comparison and treatment of time points to make the inferential question fully transparent. Those analysis details are not reported in the registry record.

Precision is another central statistical issue. A mean and standard deviation are useful summaries, but a comparative conclusion depends on an estimate and its uncertainty. Without values, intervals, or an analysis description, the reader cannot assess whether the available information was precise enough to distinguish relevant differences. Planning illustrations based on observed effects do not fill that gap and should not be confused with results or observed power.

Finally, safety counts need context. The registry records serious-event and other-event counts, but a small set of descriptive counts does not establish comparative safety. Event definitions, attribution, follow-up, and analysis are important to interpret such data. The study is informative as a record of a randomized early-phase pharmacokinetic investigation, while the absence of outcome analyses limits what can be concluded from it.

14. Limitations

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

The most direct limitation is that the registry record does not report numerical results for the primary Cmax outcome or the named Tmax outcomes. It lists 0 analyses, leaving no reported estimate, uncertainty interval, or statistical comparison to interpret. The study's pharmacokinetic question therefore remains unanswered by the results recorded in the registry.

The record does not identify the primary contrast among the three regimens or explain how Day 1 and Day 7 measurements were handled. It does not report sampling schedules, analysis models, distributional checks, missing-data procedures, or outcome-specific analysis populations. The record also does not report baseline characteristics, adherence, withdrawals, protocol deviations, or the number contributing data to each outcome.

Although the study is randomized, the record does not describe sequence generation or allocation concealment. It is unmasked, and the record does not specify who knew treatment assignments or how knowledge of assignment was managed during sampling, assessment, or analysis. These design details can matter when judging bias, but their absence does not establish that bias occurred.

The population is identified as healthy male adult volunteers, while the listed conditions are glaucoma and ocular hypertension. The record does not describe a patient population or clinical efficacy outcome. This limits the relevance of the study's concentration measures to clinical effectiveness and to populations not represented by the stated participants. The Phase 1 design and the recorded enrollment of 30 also mean the registry alone cannot establish how well the study could characterize uncommon events or generalize beyond its enrolled population.

Safety information is limited to group-level counts. Event terms and severity details for other adverse events are not reported in the registry record, and deaths are not reported there. No statistical comparison of adverse-event risk is provided.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetic Study of OPC-1085EL Ophthalmic Solution in Healthy Male Adult Volunteers — NCT02108288.
• Registry record last updated 2015-04-22; status last verified 2015-04.
• Results first posted 2015-04-02.
• 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 NCT02108288 as a completed randomized, unmasked, parallel Phase 1 study sponsored by Otsuka Pharmaceutical Co., Ltd. It enrolled 30 healthy male adult volunteers. The listed interventions were OPC-1085EL ophthalmic solution, carteolol long-acting ophthalmic solution, and latanoprost ophthalmic solution, each administered once daily; the brief summary describes treatment for 7 days.

The primary outcome was Cmax of carteolol, measured in ng/mL and summarized as a mean with standard deviation at Day 1 and Day 7. Secondary outcomes included Tmax of carteolol and Tmax of latanoprost acid. The registry record lists four outcome measures and 0 analyses, and does not report numerical pharmacokinetic results.

The registry records 0 serious adverse events among 10 participants at risk in each group. Other adverse events were reported for 6 participants in the OPC-1085EL group, 4 in the carteolol long-acting group, and 8 in the latanoprost group, with 10 at risk in each. Deaths are not reported in the registry record. The study's statistical analysis plan, missing-data approach, and analysis populations are not reported.