8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for 8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD) (NCT01451827), a randomized phase 2 study. The primary outcome is Percent Change From Baseline in Total Kidney Volume (TKV) at Week 3.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, multicenter, placebo-controlled, double-blind, placebo-masked, parallel-group pilot trial. The registry lists enrollment of 178 and a completed status. The listed start was 2011-10, and primary completion was 2013-07. The study compared tolvaptan MR 50 mg, tolvaptan MR 80 mg, and tolvaptan IR 60/30 mg with placebo.

The primary outcome was a continuous measure: percent change from baseline in TKV at Week 3. The registry defines the primary analysis population as participants who were randomized and had baseline and post-baseline observations in total renal volume. This population definition matters because enrollment and the number contributing to an endpoint can differ. The registry does not report a single primary analysis denominator in the endpoint description; group-level numbers appear with the posted outcome results.

The registry also lists change from baseline in total score on the ADPKD Urinary Impact Scale and percent change in TKV at Week 8 as secondary outcomes. The posted Week 8 TKV results include fewer participants in some groups than the Week 3 results. The reason for that difference, and how missing endpoint observations were handled, is not reported in the registry record.

Randomization and masking are features of the design intended to limit bias, but they do not by themselves establish that every comparison is precise or that all sources of bias were controlled. The registry record does not report the original sample-size justification, detailed randomization procedures, or the full protocol’s analysis plan. Those details should not be inferred from the trial’s enrollment or from the planning illustrations based on observed effects.

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: Participants entered a screening period within 4 weeks of being randomized (1:1:1:1) to one of four treatment groups. 178 is the number of subjects who enrolled due to informed consent, 177 is the number of subjects who were assigned to each treatment group.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who were randomized and had baseline and post-baseline observations in the total renal volume.

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: All participants randomized to treatment.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From Baseline in Total Kidney Volume (TKV) at Week 3, measured over Baseline to Week 3.

The primary endpoint measures the percent change in total kidney volume (TKV) from baseline to Week 3. TKV is an anatomical measure of kidney size, and the registry describes it as an important measure of disease progression. The stated rationale for the Week 3 assessment is that this time point is adequate to assess acute effects on kidney cyst shrinkage.

Percent change expresses change relative to the baseline value, allowing the endpoint to describe how kidney volume shifted over the specified interval. A negative mean indicates a decrease from baseline; a positive mean indicates an increase. This is a general interpretation of the direction of a percentage change, not a clinical judgment about its importance. TKV is a surrogate measure in this trial: the primary endpoint is not itself a direct measure of symptoms, kidney function, or a long-term clinical outcome.

The registry reports group means and standard deviations for the primary endpoint. The posted means were -2.46 for MR 50 mg, -2.55 for MR 80 mg, -1.17 for IR 60/30 mg, and 0.09 for placebo. The reported analysis population required baseline and post-baseline observations. The endpoint description does not state how missing measurements were handled or whether any additional endpoint-specific exclusions were applied.

7. Results Posted in the Registry

• Tolvaptan MR 50 mg: mean -2.46 versus 0.09 on control; difference -2.55 (95% CI -4.69 to -0.41), standardized effect d = -0.52; z-test p = 0.020.
• Tolvaptan MR 80 mg: mean -2.55 versus 0.09 on control; difference -2.64 (95% CI -4.67 to -0.61), standardized effect d = -0.57; z-test p = 0.011.
• Tolvaptan IR 60/30 mg: mean -1.17 versus 0.09 on control; difference -1.26 (95% CI -3.43 to 0.91), standardized effect d = -0.26; z-test p = 0.254.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percent Change From Baseline in TKV at Week 8.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Tolvaptan MR 50 mg: mean -2.04 versus 2.13 on control; difference -4.17 (95% CI -7.79 to -0.55), standardized effect d = -0.65; z-test p = 0.024.
  • Tolvaptan MR 80 mg: mean -2.02 versus 2.13 on control; difference -4.15 (95% CI -7.67 to -0.63), standardized effect d = -0.66; z-test p = 0.021.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Tolvaptan MR 50 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Tolvaptan MR 80 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary results cover percent change in TKV at Week 8 and change from baseline in total score on the ADPKD Urinary Impact Scale. Detailed group-level results and sponsor analyses are posted for Week 8 TKV, but the urinary-impact outcome does not have detailed results in the registry record. The Week 8 group means show a pattern in which the MR groups have negative mean changes and placebo has a positive mean change, while the IR group mean is close to zero. This is broadly consistent in direction with the Week 3 pattern, but it is a later endpoint with a different observed analysis population. It is not a direct replication of the primary result.

The posted Week 8 sponsor analyses include an overall ANCOVA ratio of geometric means of 0.97 (95% CI 0.94 to 0.99; p = 0.021) and a comparison of MR 80 mg with placebo of 0.96 (95% CI 0.93 to 1.00; p = 0.029). These results contribute context about the later TKV assessment, but they do not establish that all formulations had the same pattern or that any effect persisted beyond the reported timeframe.

Secondary outcomes generally carry less weight than a prespecified primary endpoint for confirmatory interpretation. The registry does not report a multiplicity adjustment, and multiple outcomes or comparisons increase the chance of at least one apparently notable result arising by chance. The outcome list and posted analyses are also not complete enough to establish how the sponsor planned to prioritize all secondary tests. Secondary findings are therefore most useful as supportive or exploratory evidence, interpreted alongside the primary result rather than as independent confirmation.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline in Total Score of the Autosomal Dominant Polycystic Kidney Disease Urinary Impact Scale (ADPKD-UIS)
• Percent Change From Baseline in TKV at Week 8.

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a measured quantity that can take many values rather than a simple event count. The registry reports the mean percent change and standard deviation for each group. A mean describes the group’s average observed change. A standard deviation describes how dispersed individual observations are around that average; it is not the uncertainty interval for the mean and is not a range containing every participant’s result.

What does the sponsor’s ANCOVA report?

The registry identifies ANCOVA as the method for the sponsor’s primary analyses and reports ratios of geometric means. ANCOVA is a regression-based method that can compare groups while accounting for specified covariates. Which covariates were included, how they were coded, and the model details are not reported in the registry record. The geometric-mean ratio is a different summary from a difference between arithmetic means. It should therefore be read as the sponsor’s model-based comparison on its reported scale, not as a restatement of the simple mean differences calculated from the posted group summaries.

The sponsor reports an overall four-group analysis and pairwise comparisons with placebo. The overall result addresses the model’s comparison across the listed groups; it does not by itself say that each active group differs from placebo. Pairwise results address individual formulation-versus-placebo comparisons. The registry does not report whether or how the pairwise tests were adjusted for making multiple comparisons, so the listed p-values should not be assumed to account for multiplicity.

What do the recalculations represent?

The posted recalculations compare each treatment group’s mean with the placebo mean using the group-level sample sizes and standard deviations. They are unadjusted, summary-statistic-based comparisons. They do not reproduce an ANCOVA model, do not account for covariates that may have been used in the sponsor’s analysis, and should not be treated as the sponsor’s results. The record flags a discrepancy between the recalculations and the sponsor’s results; the sponsor’s own analysis takes precedence. The recalculations can help readers see what a straightforward comparison of the displayed means implies, but they cannot establish why the analyses differ.

How should p-values be read?

A p-value measures how incompatible the observed data are with a specified statistical model in which there is no group difference, under the assumptions of that model. It is not the probability that the null hypothesis is true, nor does it measure the magnitude or clinical value of a difference. A smaller p-value is not automatically evidence of a more important effect. Interpretation also depends on the analysis plan, endpoint, study design, and the number of comparisons. The posted sponsor p-values and unadjusted recalculation p-values belong to different analyses and should not be interchanged.

Why do confidence intervals matter?

A confidence interval is a range of estimates compatible with the data and analysis under a repeated-sampling procedure. It communicates precision and the range of effects that remain plausible under the model; it is not a guarantee that the true value lies inside the particular interval. For ratios, the reference value of 1 represents no ratio difference. For differences, the reference value of 0 represents no mean difference. The sponsor’s intervals are for the reported geometric-mean ratios, while intervals from simple recalculation concern mean differences; their scales and interpretations differ.

What are the limits of these methods?

The registry record does not report the original statistical analysis plan, the covariates in ANCOVA, the handling of missing outcomes, or a multiplicity procedure. It also does not report a sample-size justification or interim-analysis plan. These omissions prevent a full assessment of whether the posted methods match the prespecified plan and how all analyses were selected. General statistical interpretation should therefore stay close to the methods and results actually reported, rather than assume unreported model choices.

11. Confidence Intervals and Precision

The sponsor’s 95% confidence intervals provide a sense of the precision of the adjusted geometric-mean ratios. For the overall primary comparison, the interval is 0.96 to 1.00. The pairwise intervals are 0.96 to 1.00 for MR 50 mg, 0.95 to 0.99 for MR 80 mg, and 0.97 to 1.01 for IR 60/30 mg. These intervals are on the ratio scale, where 1 is the reference value for no ratio difference. The interval for IR 60/30 mg includes 1, while the MR 80 mg interval does not; the MR 50 mg interval reaches 1 at its reported precision.

The interval endpoints are rounded in the registry, so they should not be treated as more exact than reported. The p-values and intervals can appear to give slightly different impressions at a threshold because they are rounded and may be based on the model’s underlying, unrounded results. The registry does not provide unrounded estimates.

Precision is also reflected in the spread of the observed group data. The posted standard deviations are 4.4 for MR 50 mg, 3.85 for MR 80 mg, 4.52 for IR 60/30 mg, and 5.31 for placebo. A standard deviation describes variability among observations, whereas a confidence interval describes uncertainty in an estimated comparison. These quantities answer different questions.

Although the sponsor’s intervals help characterize uncertainty, they do not address every source of uncertainty. The record does not report the covariates in the adjusted analysis, its missing-data assumptions, or any multiplicity adjustment. The results also concern the Week 3 TKV endpoint, not longer-term outcomes. Precision in this model-based endpoint estimate should not be confused with certainty about effects on other outcomes or over a longer period.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size planning figures are illustrations based on the observed effect, not the trial’s original design assumptions. For these continuous-outcome comparisons, the figures are participants per arm. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. The registry record does not report the trial’s original sample-size justification or its design assumptions.

The 80% power column gives the illustrative number of participants per arm for a design that would have an 80% chance of detecting the specified effect if that effect and the stated assumptions held. The 90% power column uses a higher target chance of detection, so its planning figures are larger for the listed comparisons. These are prospective planning quantities, not evidence about how likely the completed trial was to detect an effect.

Each comparison has planning illustrations for 100%, 75%, and 50% of its observed effect. The smaller the effect a future study aims to detect, the more participants per arm are generally needed under the same assumptions. The displayed figures are conditional on treating the observed effect as a planning reference; observed effects can be unstable, especially in a pilot trial. These values are not observed power. They do not revise or explain the enrollment of the completed study, and they do not substitute for an original protocol-based sample-size rationale.

For the Week 8 secondary endpoint, planning illustrations are posted only for the MR comparisons with placebo. No corresponding planning figures are posted for the IR comparison. The registry’s stated assumptions apply to the planning illustrations, not necessarily to the sponsor’s original trial design.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -2.550; pooled standard deviation σ = 4.865.
2. n = 2 × (1.96 + 0.842)² × 4.865² / -2.550² = 57.1, rounded up to 58 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -2.55                      # observed difference in means
sigma <- 4.86464455707369                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1451827)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 58 (80% power), 77 (90% power)
 75% of observed effect: n per arm = 102 (80% power), 136 (90% power)
 50% of observed effect: n per arm = 229 (80% power), 306 (90% power)
power.t.test: 58.1 
Simulated power at n = 58 per arm: 0.803 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s primary results are ANCOVA analyses reported as ratios of geometric means, with confidence intervals and p-values. The simple recalculations instead compare posted group means using summary statistics and yield unadjusted mean differences. These are distinct estimands and methods: the recalculations do not reproduce the sponsor’s adjusted model.

For the primary endpoint, the sponsor reports pairwise ratios of 0.98 for MR 50 mg, 0.97 for MR 80 mg, and 0.99 for IR 60/30 mg, with corresponding p-values of 0.015, 0.011, and 0.242. The unadjusted recalculated p-values are 0.02, 0.011, and 0.254. Similarity in some rounded p-values does not make the analyses interchangeable, while differences in estimates or significance can reflect their different methods and scales.

The registry flags a discrepancy. Accordingly, the sponsor’s own analysis takes precedence as the trial’s reported analysis. The recalculations are best treated as a transparent, unadjusted check based on the posted summaries, not as a correction to the sponsor’s results. The registry does not report enough detail about the ANCOVA covariates or analysis plan to explain fully why the estimates differ.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study assesses several outcomes, treatment groups, time points, or pairwise comparisons. If each test is interpreted on its own without accounting for the number of tests, the chance of at least one false-positive finding can increase. This is a general statistical concern; it does not show that a particular posted result is false.

The registry record lists a primary endpoint, secondary outcomes, and multiple sponsor analyses. It does not report whether the primary or secondary comparisons were adjusted for multiplicity, whether a hierarchy of tests was prespecified, or how the reported analyses were selected. The posted p-values should therefore be read as reported, without assuming that they control an overall error rate across all analyses. The absence of a reported adjustment is not proof that none was used; it means the record does not document one.

The registry defines the primary analysis population as randomized participants with baseline and post-baseline observations in total renal volume. It does not report a detailed missing-data method, the reasons for missing measurements, or whether any sensitivity analyses assessed the impact of missingness. The Week 8 group-level numbers differ from the Week 3 numbers, but the record does not explain why. It would be inappropriate to attribute that difference to a specific reason without further information.

The record also does not report the covariates used in ANCOVA, the original sample-size justification, an interim-analysis plan, or the full prespecified statistical analysis plan. These details are relevant to judging whether analyses were planned in advance and how robust they are to assumptions. The listed trial design and posted results support description of the comparisons, but not reconstruction of unreported methods.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hepatic enzyme increased (2.4%), alanine aminotransferase increased (2.3%), liver function test abnormal (2.3%), sinus tachycardia (2.2%), blood creatinine increased (2.2%).

The registry reports serious adverse events by group, with the number at risk and the number affected. Serious adverse events affected 3 participants in the MR 50 mg group, 1 in the MR 80 mg group, 1 in the IR 60/30 mg group, and 1 in the placebo group. The corresponding numbers at risk were 45, 44, 44, and 42. No deaths were reported in any group.

These are descriptive counts from the trial record. They do not, on their own, establish whether a difference between groups is meaningful or attributable to treatment. The record also lists percentages for serious-event terms, including hepatic enzyme increased (2.4%), alanine aminotransferase increased (2.3%), liver function test abnormal (2.3%), sinus tachycardia (2.2%), blood creatinine increased (2.2%), and dehydration (2.2%). The record excerpt does not provide group-specific counts for each listed term, so those percentages should not be assigned to a particular treatment group.

Other adverse events were reported in 27, 25, 32, and 18 participants in the MR 50 mg, MR 80 mg, IR 60/30 mg, and placebo groups, respectively. These descriptive figures do not replace a complete assessment of event definitions, timing, severity, or exposure. The registry record does not report detailed comparative safety analyses in the information presented.

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

The results describe short-term changes in TKV in a randomized, placebo-controlled Phase 2 pilot trial. At Week 3, the posted means were negative in each tolvaptan group and close to zero in the placebo group. The sponsor’s ANCOVA reported ratios of geometric means for the overall and pairwise comparisons. Together, these results describe the trial’s measured endpoint and the statistical uncertainty reported for those analyses.

They do not establish that any formulation improves how participants feel, functions, or survives, because the primary outcome was TKV change over a short interval. The registry identifies TKV as an important measure of disease progression and gives acute cyst shrinkage as the rationale for the Week 3 timing; it does not report evidence in this record connecting the observed short-term changes to later clinical outcomes. The results do not show how durable any measured change may be.

Nor do the results establish that the formulations are equivalent. A non-significant comparison is not proof that two groups are the same; it can also reflect uncertainty or limited information. The trial’s pilot designation, endpoint population, and reported group sizes are relevant context, while the registry’s missing analysis details constrain fuller interpretation. Likewise, a statistically notable result is not by itself a measure of clinical importance.

The sponsor’s adjusted analyses and simple recalculations are not interchangeable. Because the registry flags a discrepancy, the sponsor’s analysis takes precedence for the reported trial inference. The unadjusted calculations can be read as comparisons of the posted summary statistics, with different assumptions and estimands. Any conclusion should remain specific to the endpoint, comparison, time point, and analysis actually reported.

The safety figures are also descriptive. Serious adverse events and other adverse events were recorded in the groups, and no deaths were reported. Those counts alone do not establish comparative safety, particularly without additional detail on event definitions, exposure, and analysis. Overall, this record supports a careful account of short-term measurements and their uncertainty, not broad claims about treatment effects beyond the outcomes and time points recorded.

18. Why This Trial Matters Statistically

This trial is statistically informative because it places several formulations and a placebo within a randomized, masked, parallel-group design and reports both adjusted sponsor analyses and group-level summaries. That combination allows readers to distinguish the primary model-based comparisons from straightforward unadjusted calculations, rather than treating every estimate as if it came from the same method.

It also illustrates why the scale of an effect matters. The sponsor reports geometric-mean ratios, while recalculations from group means produce mean differences. These summaries answer related but distinct questions, and their numerical values should not be directly substituted for one another. The registry flags a discrepancy, reinforcing the need to identify which analysis is being interpreted and to give precedence to the sponsor’s analysis for the trial’s reported inference.

The Week 3 and Week 8 TKV endpoints make the role of time point visible: a later measurement is related to, but not identical with, the primary endpoint. The posted secondary results can add context without replacing the primary question. Missing detail about multiplicity, missing observations, model covariates, and the original sample-size rationale also demonstrates how incomplete registry reporting limits statistical evaluation, even when estimates and confidence intervals are available.

Finally, the planning illustrations show how sample-size requirements depend on the effect targeted and the assumptions used. They are useful for thinking about future study planning, but they do not reveal the trial’s original design rationale or convert the completed study into a design with a known probability of detecting its observed effect. The central statistical lesson is to keep design, endpoint, method, uncertainty, and scope of inference connected.

19. 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 registry record is limited in several trial-specific ways. It describes the primary endpoint population as randomized participants with baseline and post-baseline TKV observations, but does not detail the missing-data method, the reasons observations may be absent, or sensitivity analyses. Week 8 group-level results include different numbers of observations from the Week 3 results, and the record does not explain that difference.

The sponsor’s primary analysis is identified as ANCOVA, but the covariates and other model specifications are not reported. The record also does not report a multiplicity strategy for the several outcomes and comparisons, or the original sample-size justification. These gaps limit assessment of prespecification and the robustness of inferences from the posted p-values.

The study is described as a pilot trial and focuses on short-term TKV change. The results therefore have a narrower scope than long-term clinical outcomes. The registry lists the urinary-impact scale as a secondary outcome but does not include detailed results for it in the posted outcome information summarized in this record. Safety data are presented as group counts and selected event-term percentages, without detailed comparative analyses in the information reported.

The record flags a discrepancy between the sponsor’s analyses and simple unadjusted recalculations from summary statistics. The sponsor’s own analysis takes precedence, but the available information does not explain the discrepancy. These limitations do not negate the posted results; they define what can and cannot be assessed from the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: 8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD) — NCT01451827.
• Registry record last updated 2018-09-27; status last verified 2018-08.
• Results first posted 2018-08-13.
• 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.

23. Record Summary

The registry describes a completed Phase 2 randomized, multicenter, placebo-controlled, double-blind, placebo-masked, parallel-group pilot trial in ADPKD, with enrollment of 178. It compared tolvaptan MR 50 mg, tolvaptan MR 80 mg, and tolvaptan IR 60/30 mg with placebo. The primary endpoint was percent change from baseline in TKV at Week 3.

The sponsor reported ANCOVA analyses as ratios of geometric means, including an overall comparison and comparisons of each formulation with placebo. The registry also posts group means and standard deviations, secondary Week 8 TKV results, and adverse-event counts. The record flags a discrepancy between the sponsor’s analyses and simple recalculations; the sponsor’s analysis takes precedence.

Important details, including the original sample-size justification, missing-data methods, multiplicity plan, and ANCOVA covariates, are not reported in the registry record. The findings describe short-term TKV measurements and should be interpreted within that scope.