A Trial of OPC-41061 in Patients With Hepatic Edema - Investigation of the Safety of Treatment at 7.5 mg Beyond 7 Days and of the Effect of Dose Escalation to 15 mg: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial of OPC-41061 in Patients With Hepatic Edema - Investigation of the Safety of Treatment at 7.5 mg Beyond 7 Days and of the Effect of Dose Escalation to 15 mg (NCT01048788), a na phase 3 study. The primary outcome is Body Weight.

2. Clinical Question

The clinical question is therefore about body-weight change and safety during a short course of OPC-41061 with a treatment path that could continue at the starting dose or escalate. It is not a randomized test against standard care or placebo. Any body-weight change during follow-up would be an observation made while participants received the study drug; without a control group, the record cannot isolate the drug's contribution from other influences or establish what would have happened without treatment.

3. Trial Design

The registry identifies NCT01048788 as a completed Phase 3 trial sponsored by Otsuka Pharmaceutical Co., Ltd. It began in 2009-12, and primary completion was recorded in 2011-08. The trial title describes investigation of safety beyond 7 days at 7.5 mg and the effect of escalation to 15 mg. Its official title characterizes it as multicenter, uncontrolled and open-label. Allocation is listed as not applicable, and the model is single-group.

The registry summary describes oral OPC-41061 at 7.5 mg/day during the initial 7 days. At Day 7, body-weight change was used to decide whether to continue at 7.5 mg/day or increase to 15 mg/day for an additional 7 days if the initial diuretic effect was insufficient. Thus, the later treatment paths arose from a decision based on response, rather than assignment to randomized arms. The registry reports groups described as discontinued or terminated before Day 8, continued administration at 7.5 mg/day, and dose escalation to 15 mg/day. These categories should not be treated as exchangeable comparison groups.

Open-label means that treatment was not masked according to the registry. In general, knowledge of treatment can influence behavior, care, reporting and assessments, although the record does not describe whether or how such influences were assessed. An uncontrolled design can describe what was observed during treatment, but cannot estimate a treatment contrast against a concurrent control group. Further details about recruitment, site conduct, protocol deviations and the reasons participants discontinued or followed each treatment path 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

Reasons for not completing this period:

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 Body Weight, measured over Baseline, Day 14 or end of administration.

The registered primary endpoint is change in body weight from baseline at the end of administration. It is expressed in kilograms and characterized as a mean with standard deviation. The listed timeframe is baseline and Day 14 or end of administration. The registry summary also describes using body-weight change at Day 7 to guide whether the dose would continue or increase.

Body weight is a continuous measure: its values can vary across a range rather than being limited to categories. In general, a continuous endpoint can retain information about the magnitude of observed changes, while a mean gives a summary of the group’s values. A standard deviation describes variation among those values; it is not the same as the uncertainty around the mean. Neither measure, by itself, explains why weight changed.

In this trial, body weight was relevant to the treatment decision described in the registry and was also the primary outcome measure. The measure could describe change over the treatment period, but the uncontrolled design limits causal interpretation. The numerical mean change, its standard deviation, the number contributing to the endpoint and any confidence interval are not reported in the registry record. Consequently, the primary endpoint’s observed direction, magnitude and precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous body weight, expressed in kilograms. The registry characterizes the endpoint as a mean with standard deviation. In general, a mean summarizes the center of a set of measurements, while the standard deviation describes how spread out individual measurements are around that mean. They answer different questions: the mean concerns the average level or change, and the standard deviation concerns variability among observations. The standard deviation is not a confidence interval and does not directly show how precisely the mean has been estimated.

For a change-from-baseline endpoint, each participant's follow-up measurement is interpreted in relation to that participant's baseline measurement, and a group summary can describe the average change. In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. It indicates a range of values compatible with the data and method; it does not guarantee that the true value lies within a particular interval, nor does it resolve bias from the design. No numerical primary endpoint estimate or confidence interval is reported in the registry record, so the size and precision of the body-weight change cannot be evaluated.

The listed endpoint timeframe is baseline and Day 14 or end of administration. The registry summary separately describes a Day 7 body-weight change as part of the dose decision. Those roles should not be conflated: the registered primary endpoint is change at the end of administration, while the summary says the earlier change informed continuation or escalation. The detailed rule used for the Day 7 decision beyond the description in the summary is not reported in the registry record.

The study is described as single-group, open-label and uncontrolled, with allocation recorded as not applicable. In general, random allocation helps balance measured and unmeasured characteristics between treatment groups on average. It is not present in the design. A comparison between the recorded continuation and escalation paths would be especially difficult to interpret because the summary says escalation followed insufficient initial diuretic effect. The decision process links group membership to participants' response, so the groups do not function as randomized treatment arms.

In general, an uncontrolled study can summarize outcomes observed during treatment, but cannot directly estimate what the same participants' outcomes would have been under a different treatment or no study treatment. This distinction is important even when an outcome changes from baseline: time trends, concurrent care, measurement conditions and other influences may also contribute. The registry record does not provide a control-group result or describe an adjusted causal analysis. It reports no analyses in the information available for this account, and a statistical analysis plan is not reported in the registry record.

The record's sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. These are assumptions for planning illustrations, not evidence about how this trial was designed or analyzed. In particular, equal allocation between two arms does not describe the registered single-group design. The trial's sample-size justification is not reported in the registry record. Planning illustrations are not observed power and do not make a missing endpoint estimate available.

In general, standard deviations and uncertainty estimates can be sensitive to the shape of the outcome distribution and the analysis assumptions. Over-dispersion means that observed variability is greater than a model expects; if not addressed when relevant, standard errors and resulting intervals or tests may be unreliable. This is a general statistical consideration, not a reported finding about this trial. Distributional diagnostics, model details and any adjustment for over-dispersion are not reported in the registry record.

The safety figures are organized by treatment-path categories and distinguish serious-event figures from other adverse-event figures. In general, a count of affected participants and a count of events are not interchangeable: a participant may experience more than one event. The registry fields indicate affected counts and numbers at risk for the listed categories, but the detailed event-level definitions and methods for attribution are not reported in the registry record. The listed serious-event terms have percentages, but term-specific denominators are not reported in the registry record. Therefore, those percentages should be read as registry-listed values rather than used to derive unreported denominators or comparative risks.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Discontitued/Terminated Before Day 8", "Continued Administration at 7.5 mg/Day", "Dose Escalation to 15 mg/Day")
n   <- c(8, 30, 13)
m   <- c(-0.76, -2.97, -0.05)
sp  <- c(0.93, 2.57, 2.3)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Discontitued/Terminated Before Day 8  8  -0.760  0.930  -1.537  0.017
CARM  Continued Administration at 7.5 mg/Day  30  -2.970  2.570  -3.930  -2.010
CARM  Dose Escalation to 15 mg/Day  13  -0.050  2.300  -1.440  1.340

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary outcome measure, change in body weight from baseline at the end of administration. It does not describe a multiplicity adjustment, a hierarchy of outcomes or a prespecified approach to controlling the chance of false-positive findings across multiple tests. These details are not reported in the registry record. Since primary endpoint results and inferential analyses are also not reported in the record, there is no basis for describing how multiple testing was handled in any results analysis.

Missing-data methods are not reported in the registry record. The record does not explain how the primary endpoint was handled for participants without an end-of-administration measurement, whether measurements after discontinuation were collected, or whether any imputation or sensitivity analysis was used. The adverse-event categories include participants described as discontinued or terminated before Day 8, but the reasons for this category and its implications for endpoint availability are not reported in the registry record. It would be inappropriate to assume that missing endpoint values were absent, imputed or handled in any particular way.

Analysis populations are also not described. The registry record does not identify whether the primary analysis used all enrolled participants, only those who received treatment, participants with available endpoint measurements, or another population. It does not report whether participants were analyzed according to a prespecified population or how deviations from the intended treatment sequence were handled. The numerical endpoint results, analysis population, missing-data strategy and statistical analysis plan are not reported in the registry record, limiting assessment of both the analysis and the possible influence of incomplete follow-up.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: positional vertigo (12.5%), hernia obstructive (12.5%), muscular weakness (12.5%), diabetic neuropathy (12.5%), hepatic encephalopathy (12.5%).

The registry lists safety figures under three treatment-path categories: discontinued or terminated before Day 8, continued administration at 7.5 mg/day, and dose escalation to 15 mg/day. For serious adverse events, the figures are 3 affected among 8 at risk, 3 among 30, and 2 among 13, respectively. For other adverse events, the figures are 7 among 8, 22 among 30, and 7 among 13, respectively. These are descriptive figures for the categories recorded by the registry.

The categories should not be interpreted as randomized dose groups. The summary says the choice between continuing and escalating depended on the initial diuretic effect, and one category describes discontinuation or termination before Day 8. Differences between categories could reflect selection into each path and other factors, not just dose. The registry also lists Positional Vertigo, Hernia Obstructive, Muscular Weakness, Diabetic Neuropathy, Hepatic Encephalopathy and Polyneuropathy Alcoholic, each with 12.5%. The denominator for each listed term is not reported in the registry record. Death figures are not reported in the registry record.

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

The record establishes that a Phase 3, open-label, uncontrolled trial of OPC-41061 was completed and identifies its primary endpoint as body-weight change from baseline at the end of administration. It also describes a treatment sequence beginning at 7.5 mg/day and continuing for an additional 7 days at that dose or at 15 mg/day, depending on the initial diuretic effect. These details define the trial question and design, but do not supply the primary endpoint result.

Because the numerical primary endpoint results are not reported in the registry record, no statement can be made from this record about the observed mean change, its variability or its precision. The absence of a comparator further limits interpretation: a within-group change, if reported, would not alone establish what portion was caused by treatment. The recorded continuation and escalation paths are not like-for-like control groups because the dose decision followed participants' initial response.

The adverse-event figures describe events recorded in the treatment-path categories. They are not, by themselves, causal evidence about OPC-41061, and they do not provide a randomized comparison of safety across doses. The percentages attached to the listed serious-event terms lack reported denominators in the registry record. The record also does not report death figures or enough detail to assess the completeness of safety ascertainment.

Accordingly, the registry record supports a description of the design, endpoint definition and recorded adverse-event counts, but it does not support a quantitative conclusion about the primary body-weight outcome or a controlled estimate of treatment effect. It also does not establish how the missing endpoint results, if any, were handled or which analysis population was used. Those gaps constrain what can be concluded from the record; they should not be filled by assumptions about the protocol or the unreported results.

14. Why This Trial Matters Statistically

This trial is statistically notable because its treatment paths depend on an early response assessment rather than random assignment. The registry summary says Day 7 body-weight change informed the decision to continue at 7.5 mg/day or increase to 15 mg/day if the initial diuretic effect was insufficient. Consequently, the later groups reflect both the treatment received and the decision process that placed participants in those groups. Treating them as comparable arms would ignore this selection.

The uncontrolled design also illustrates the difference between describing change and estimating a treatment effect. A baseline-to-follow-up change can describe what happened during a study period, but without a concurrent comparator it does not isolate the contribution of treatment from other influences. That distinction remains important regardless of whether an outcome is clinically familiar or measured on a continuous scale.

The record's primary endpoint is clearly identified as mean change in body weight, but its numerical results are not reported in the registry record. This gap prevents assessment of the observed effect and its precision. The safety figures offer descriptive counts organized by treatment path, but they do not overcome the lack of randomization or create a valid dose comparison. The term-specific percentages also lack reported denominators in the record.

Finally, the stated planning assumptions describe an illustration based on the observed effect and a hypothetical two-arm equal-allocation setup. Such assumptions should be distinguished from the actual single-group design and from observed evidence. The record is a useful example of why design, treatment selection, endpoint reporting and analysis details all matter when interpreting clinical trial statistics.

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.

Several limitations specific to this trial follow from the registry record. The study was uncontrolled and open-label, with no randomized comparator described. The continuation and escalation categories resulted from a response-dependent treatment decision, so they cannot be treated as like-for-like groups for estimating a dose effect. The trial's single-group structure also prevents a direct concurrent comparison with another treatment or with no study treatment.

The registry identifies body-weight change as the primary endpoint but does not report its numerical result, standard deviation, confidence interval or analysis population. The endpoint's observed magnitude and precision therefore cannot be assessed. Although the summary describes body-weight change at Day 7 as relevant to treatment decisions, the detailed decision rule is not reported in the registry record.

Analysis details are limited: a statistical analysis plan, missing-data methods, multiplicity procedures, protocol deviations and analysis populations are not reported in the registry record. The adverse-event figures are divided into treatment-path categories, but the record does not establish that all categories were observed over equivalent periods or explain the detailed event-collection and attribution methods. The denominator for each listed serious-event term is not reported in the registry record, and death figures are not reported in the registry record. These omissions limit interpretation of both efficacy and safety without supporting assumptions about unreported methods or results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Trial of OPC-41061 in Patients With Hepatic Edema - Investigation of the Safety of Treatment at 7.5 mg Beyond 7 Days and of the Effect of Dose Escalation to 15 mg — NCT01048788.
• Registry record last updated 2016-04-11; status last verified 2016-03.
• Results first posted 2014-03-04.
• 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

NCT01048788 is a completed, open-label, uncontrolled Phase 3 trial sponsored by Otsuka Pharmaceutical Co., Ltd. The record describes oral OPC-41061 in patients with cirrhosis and ascites despite conventional diuretic therapy. Treatment began at 7.5 mg/day for 7 days, followed by continuation at that dose or escalation to 15 mg/day for an additional 7 days based on the initial diuretic effect.

The registered primary endpoint is mean change in body weight from baseline at the end of administration, with standard deviation and a timeframe of baseline and Day 14 or end of administration. Numerical primary endpoint results are not reported in the registry record. Safety figures are listed for the recorded treatment-path categories, but those categories are not randomized comparisons. The registry record does not report the analysis population, missing-data methods or statistical analysis plan.