Investigation of the Superiority Effect of Orally Disintegrating Desmopressin Tablets to Placebo in Terms of Night Voids Reduction in Nocturia Adult Male Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation of the Superiority Effect of Orally Disintegrating Desmopressin Tablets to Placebo in Terms of Night Voids Reduction in Nocturia Adult Male Patients (NCT01262456), a randomized phase 3 study. The primary outcome is Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, double-blind, placebo-controlled, parallel-group trial in adult males with nocturia. The registry lists an enrollment of 395. The double-blind treatment period lasted 3 months and compared nightly desmopressin orally disintegrating tablets at 50 μg or 75 μg with placebo. The stated timing was approximately 1 hour before bedtime.

The record also describes an open-label extension. Participants completing the double-blind period were switched to desmopressin 100 μg for the 1-month extension, including those assigned to placebo during the blinded period. Since treatment in the extension was open-label and the placebo group crossed to active treatment, extension observations do not provide the same blinded placebo comparison as the main treatment period.

The trial’s brief summary describes its purpose as confirming or establishing long-term safety and efficacy at 50 μg and 75 μg, and further evaluating the safety of an efficacious higher dose of 100 μg. That statement describes the trial’s stated purpose; it is not a report of the findings. The primary endpoint description identifies change in nocturnal voids as the first co-primary outcome and says superiority to placebo was to be demonstrated on both co-primary outcomes. The second co-primary outcome is not identified in the available registry record.

The primary outcome was based on participant diary recordings. The registry describes measurements at baseline, Week 1, and Months 1, 2, and 3. The record does not report the allocation ratio, the number assigned to each double-blind arm, or further details of the randomization process. Specific eligibility criteria beyond adult males with nocturia 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.

Before assignment: A total of 1013 participants were screened; 618 were screening failures and 395 were randomized. The most common reason for screening failure was non-fulfillment of inclusion/exclusion criteria (535 participants); 23 participants withdrew consent prior to randomization and 60 participants had other reasons for screening failure.

3-Month Double-Blind Period

Reasons for not completing this period:

1-Month Open-Label Extension Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS).

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.

Population: Demographic data offered from the Full Analysis Set population.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Mean Number of Nocturnal Voids Averaged Over a 3-Month Period, measured over Day 1 (Baseline), Week 1, Months 1, 2, 3 (3-month double-blind treatment period).

The primary endpoint was change from baseline in the mean number of nocturnal voids averaged over a 3-month period. Nocturnal voids were averaged over 3 consecutive 24-hour periods before Day 1 and before the during-treatment visits. The first morning void was not counted. Participant diaries were the stated source of these measurements.

This endpoint represents a repeated measure of nighttime void frequency rather than a single observation. The record says the comparison of baseline and treatment-period mean values was obtained through longitudinal analysis of measurements at Week 1 and Months 1, 2, and 3. A change-from-baseline measure expresses the treatment-period outcome relative to the participant’s baseline value; the endpoint description does not itself establish the direction or size of any treatment effect.

In general, repeated measurements can describe how an outcome changes during follow-up and can use observations from more than one visit. The clinical reason for selecting nocturnal void frequency as the primary endpoint is not explained in detail in the registry record. The record identifies the analysis population as the full analysis set (FAS), and specifies the endpoint’s unit as nocturnal voids. It does not report the primary endpoint’s group estimates, variability, confidence intervals, or significance tests. Those results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a longitudinal analysis of nocturnal void measurements collected at Week 1 and Months 1, 2, and 3. It says the comparison involved mean values at baseline and over the 3-month treatment period. It does not provide the model specification, the estimated treatment contrasts, or the test results. The explanation below describes general statistical concepts relevant to this design, not additional methods confirmed for the trial.

What does longitudinal analysis mean?

In general, longitudinal analysis concerns repeated observations made on the same participants over time. Measurements from one participant are usually related to one another, so they should not automatically be treated as independent observations. An analysis can account for that within-participant relationship while comparing the patterns or average outcomes across randomized groups. The registry identifies the analysis as longitudinal but does not state which particular model, covariance structure, or estimation procedure was used. Those details are not reported in the registry record.

A repeated-measures approach can use information from multiple scheduled visits rather than treating each visit as an unrelated experiment. The interpretation still depends on the model, the data included, and how missing observations are handled. Without the model details and the reported estimates, it is not possible to reconstruct the primary comparison or assess whether the assumptions were appropriate.

What does a mean change describe?

In general, a mean is an average across observed values. A mean change compares a participant’s outcome after baseline with that participant’s baseline value, and a group summary then describes those changes across the analyzed participants. A mean can be informative about the average outcome, but it may not show how much participants’ responses vary or whether the average reflects a broadly similar pattern across individuals. The primary endpoint specifies standard deviation as its dispersion measure, but the record does not report the endpoint’s group means, changes, or standard deviations.

In general, a standard deviation describes the spread of observations around their mean. It is not the same as a standard error, which describes uncertainty in an estimated quantity. A confidence interval is often used to communicate the uncertainty around a treatment contrast. Neither a confidence interval nor a standard error can be inferred from the endpoint description alone. The registry record does not report these primary outcome statistics.

How should a treatment comparison be read?

In general, a treatment comparison should be read through its estimated between-group contrast, its uncertainty, and the analysis definition. The direction of a contrast depends on how it is calculated and presented. The endpoint name says “change from baseline,” but the registry record does not provide the sign convention or actual estimates. It is therefore not possible to state the direction or size of a difference from the information available.

A confidence interval, in general, gives a range of values compatible with the observed data under the statistical method and assumptions. A narrow interval indicates greater precision than a wide interval, while an interval spanning values in opposing directions may leave the direction of the effect uncertain. These interpretations require an actual estimate and interval. Neither is reported for the primary endpoint in the registry record.

A p-value, in general, describes the compatibility of the observed data with a null hypothesis under a specified statistical model. It does not state the probability that the null hypothesis is true, and it does not measure the clinical importance of an effect. The registry describes a nominal significance level for controlling the family-wise error rate, but provides no primary endpoint p-values. The planned testing approach therefore cannot be used to infer whether any comparison passed its criterion.

Why is the testing order relevant?

The registry says superiority to placebo was to be demonstrated on both co-primary outcomes using a step-down approach from the 75 μg dose to the 50 μg dose, controlling the family-wise error rate at the 5% nominal significance level. In general, testing more than one hypothesis can increase the chance of at least one false-positive result if each test is treated as an independent opportunity for significance. A multiplicity procedure sets out how the tests are ordered or adjusted to manage that overall error risk.

A step-down procedure generally tests hypotheses in a specified sequence, with later tests depending on the outcome of earlier tests. Here, the stated order begins with the higher dose and moves to the lower dose, and the registry states that both co-primary outcomes had to support superiority. However, the complete testing details, including the identity of the second co-primary endpoint and the specific decision rules, are not reported in the registry record. The primary estimates and test outcomes are also absent, so the multiplicity procedure’s application cannot be assessed from the posted results.

What role does over-dispersion play?

In general, over-dispersion occurs when data vary more than a chosen statistical model expects. If a model fails to account for that extra variation, standard errors can be too small and confidence intervals can be too narrow. Methods that accommodate over-dispersion can improve uncertainty estimates for outcomes whose variability exceeds the model’s assumptions. The registry identifies the primary endpoint as a mean of a continuous measure and describes a longitudinal analysis; it does not state that over-dispersion was assessed or that a model requiring an over-dispersion adjustment was used. Its relevance to this analysis is therefore not reported in the registry record.

Can the analysis be independently checked?

In general, an independent check of a reported result needs sufficient detail about the analyzed observations, model, contrast, uncertainty, and handling of missing data. The registry record names the FAS and reports the visit schedule and broad analysis approach, but does not provide the primary outcome statistics or detailed model specification. Missing-data procedures and sensitivity analyses are not reported in the registry record. The posted information consequently allows a high-level description of the intended endpoint analysis, but not a recalculation or a full assessment of its statistical assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry explicitly addresses multiplicity for the primary efficacy testing. It identifies the nocturnal-void endpoint as the first co-primary outcome and states that superiority to placebo was to be demonstrated on both co-primary outcomes. Testing was to proceed in a step-down approach from 75 μg to 50 μg, with family-wise error controlled at the 5% nominal significance level. The second co-primary outcome and the detailed decision rules are not reported in the registry record. Neither the primary tests nor their results are reported, so it is not possible to determine whether the planned sequence was completed or whether its criteria were met.

The registry lists secondary outcomes, including changes in nocturnal voids, time to first nocturnal void, urine volumes, adverse events, and minimum post-treatment serum sodium levels. It does not state how multiplicity was handled for those secondary outcomes. Their inclusion in the record should not be taken as evidence that each was confirmatory or that any particular adjustment was used.

The primary outcome description specifies the full analysis set (FAS), but does not define the set or report how participants were included in each visit’s analysis. Details about missing observations, withdrawals, imputation, or sensitivity analyses are not reported in the registry record. General statistical practice recognizes that missing-data assumptions can affect estimates, particularly when the probability of an observation being missing is related to its outcome. Without the trial’s procedures and relevant results, the effect of missingness cannot be assessed.

The registry reports an overall enrollment of 395, but that figure does not identify the number analyzed for the primary endpoint. The group-specific counts shown for adverse-event summaries refer to those safety summaries and should not be treated as primary efficacy analysis denominators.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hyponatraemia (3.3%), acute myocardial infarction (0.8%), osteoarthritis (0.8%), transient global amnesia (0.8%), rib fracture (0.8%).

The registry reports serious-event and other-event counts separately for the double-blind groups and for groups described as continuing into the open-label period. For the double-blind period, the serious-event counts were 4 among 119 at risk in the 50 μg group, 5 among 122 at risk in the 75 μg group, and 1 among 143 at risk in the placebo group. The corresponding other-event counts were 6 among 119, 7 among 122, and 5 among 143.

For the groups extending into the open-label period, the serious-event counts were 0 among 101 at risk for the 50 μg / 100 μg group, 1 among 102 at risk for the 75 μg / 100 μg group, and 2 among 124 at risk for the placebo / 100 μg group. The other-event counts were 0 among 101, 0 among 102, and 1 among 124, respectively. These are registry counts for the listed periods and groups; they should not be combined across periods or treated as a comparison that preserves blinding.

The registry also lists selected serious-event terms with percentages, including Hyponatraemia at 3.3% and several terms at 0.8% or 0.7%. The percentage denominators and further context for those terms are not reported in the registry record. Death counts are recorded as null for the listed groups, so death results are not reported in the registry record. These summaries do not establish comparative risk or replace a complete safety analysis.

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

The record establishes that the trial was designed to compare desmopressin 50 μg and 75 μg with placebo during a 3-month double-blind period in adult males with nocturia. It identifies change from baseline in mean nocturnal voids as a co-primary endpoint and describes diary-based measurement and a longitudinal analysis. It also states that both co-primary outcomes were to support superiority to placebo within a step-down testing approach.

Those design details do not tell readers what the treatment effect was. The group estimates, treatment contrasts, confidence intervals, and p-values for the primary endpoint are not reported in the registry record. The second co-primary outcome is not identified in the available record. Therefore, the posted information does not establish whether the planned primary comparisons favored either treatment, how large any difference was, or how precise the estimates were.

In general, statistical evidence about an effect combines the estimated difference with its uncertainty and the analysis context. A result can be statistically compatible with a difference while still leaving its size imprecise, or it can be estimated precisely without establishing clinical importance. Those distinctions require the numerical results and relevant context, which are not reported in the registry record.

The safety summaries are descriptive counts for the stated groups and periods. They do not, on their own, establish whether the treatments differ in safety. The open-label period followed a switch to desmopressin 100 μg among participants completing the blinded period, so it does not provide a continuing randomized placebo comparison. Selected adverse-event percentages are reported without their denominator basis in the available record, and death results are not reported.

The appropriate reading is consequently limited: the record describes the trial’s design, endpoint, planned multiplicity approach, and selected safety counts. It does not supply enough primary efficacy results to determine the direction, magnitude, or precision of the treatment comparison. It also does not provide enough detail to assess the full analysis model, missing-data handling, or all safety findings.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a design with multiple active doses, a placebo comparator, repeated outcome measurement, and co-primary testing. Each feature affects how results should be interpreted. Randomization and double-blinding define the intended comparison during the main treatment period; repeated diary measurements form the basis of the primary endpoint; and the stated step-down procedure addresses the risk associated with testing co-primary outcomes and dose comparisons.

The registry also illustrates why a detailed endpoint description is not a substitute for an effect estimate. It specifies the outcome, its unit, measurement schedule, and broad analysis approach, but does not report the primary results. Without estimates and uncertainty measures, readers cannot judge the size or precision of the primary comparison. Knowing that a statistical plan was intended does not reveal whether its criteria were met.

The open-label extension matters when distinguishing evidence types. Participants completing the blinded period were switched to 100 μg, including those initially assigned to placebo. That extension may contribute to the trial’s stated safety purpose, but it does not preserve the blinded placebo comparison. The periods therefore need to be read as different parts of the design rather than as interchangeable treatment comparisons.

Finally, multiplicity and analysis-population details are central to a careful reading. The record states a family-wise error approach for the co-primary efficacy tests, but the second endpoint and detailed test results are not available. It identifies the FAS without defining it or explaining missing-data procedures. These omissions limit independent assessment of the analysis. The statistical importance of the trial lies not only in the questions its design addresses, but also in recognizing what the posted record does and does not allow readers to conclude.

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 main limitation for interpreting efficacy is that the registry record does not report primary outcome estimates, variability, confidence intervals, or p-values. Although it describes a longitudinal analysis and identifies the FAS, the model specification and the analyzed participant counts are not reported. The second co-primary outcome is not identified in the available record, and the reported results do not establish whether the planned superiority criteria were met.

The record does not describe missing-data methods, the reasons for missing observations, or sensitivity analyses. It also does not define the FAS. These omissions prevent assessment of how incomplete diary data or other missing outcomes might have affected the primary analysis. Details of the randomization procedure, allocation ratio, and eligibility criteria beyond adult males with nocturia are not reported in the registry record.

The extension was open-label, and participants completing the blinded period were switched to desmopressin 100 μg. The extension therefore should not be interpreted as a continuation of the randomized placebo comparison. The available safety summaries provide counts for specified groups, but do not present a complete account of adverse events. The basis for the listed serious-event percentages is not reported, and death results are not reported in the registry record.

The registry states that efficacy testing was to follow a step-down approach and control family-wise error at the 5% nominal significance level, but the second co-primary outcome and full decision rules are unavailable. Multiplicity handling for secondary outcomes is not reported. These limitations mean the record supports a description of the design and selected safety summaries, but not a complete appraisal of efficacy, precision, or the full statistical analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Investigation of the Superiority Effect of Orally Disintegrating Desmopressin Tablets to Placebo in Terms of Night Voids Reduction in Nocturia Adult Male Patients — NCT01262456.
• Registry record last updated 2015-10-15; status last verified 2015-09.
• Results first posted 2015-10-15.
• 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 record describes a Phase 3 randomized, double-blind, placebo-controlled, parallel-group trial in adult males with nocturia, with enrollment of 395. During the 3-month blinded period, participants received nightly desmopressin 50 μg, desmopressin 75 μg, or placebo. Participants completing that period were switched to desmopressin 100 μg for a 1-month open-label extension.

The first co-primary outcome was change from baseline in mean nocturnal voids, measured using participant diaries and analyzed longitudinally across treatment visits. The record describes a step-down superiority-testing approach across doses and co-primary outcomes. It does not report the primary outcome estimates or test results, and the second co-primary outcome is not identified in the available record.

Selected safety counts are reported for the blinded and open-label periods. Detailed model specifications, missing-data methods, and several other analysis details are not reported in the registry record.