This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Short-term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (NCT01336972), a non-randomized phase 2 study. The primary outcome is Mean Change From Baseline in Measured Glomerular Filtration Rate (mGFR) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01336972 |
| Phase | Phase 2 |
| Condition | Autosomal Dominant Polycystic Kidney Disease |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 29 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Otsuka Pharmaceutical Development & Commercialization, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants had autosomal dominant polycystic kidney disease (ADPKD) and were enrolled across three renal-function groups: eGFR > 60 mL/min/1.73m2, eGFR 30 to 60 mL/min/1.73m2, and eGFR < 30 mL/min/1.73m2. The primary endpoint population was narrower than all enrolled participants: it included those who took any trial medication and had a postbaseline renal-function test.
Intervention
Participants received oral tolvaptan during the first 3 weeks of a 6 week study. The regimen was increased weekly from 45/15 mg to 60/30 mg to 90/30 mg, with AM and PM split doses 8 hours apart, up to the maximally tolerated dose.
Comparator
No placebo or untreated control group is described. The three groups were defined by renal-function category, and each group received tolvaptan. This is a non-randomized, unmasked, parallel study, so the groups are not like-for-like treatment and control arms.
Primary question
The primary question concerned mean change from baseline in measured glomerular filtration rate (mGFR) after 3 weeks of tolvaptan treatment and at 3 weeks post treatment. The endpoint captures short-term renal hemodynamic measurements during exposure and after treatment ended. Numerical estimates of this change are not reported in the registry record, so the direction and precision of the observed mGFR changes cannot be assessed from the record.
3. Trial Design
This was a Phase 2a, single-center study of oral tolvaptan in participants with ADPKD at various stages of renal function. The registry lists an enrollment of 29 and describes the study as completed. It began in 2010-10, with primary completion in 2011-11. The allocation was non-randomized, masking was none, and the model was parallel.
Participants were assigned to groups based on eGFR: Group A had eGFR > 60 ml/min/1.73m^2, Group B had eGFR 30 to 60 ml/min/1.73m^2, and Group C had eGFR < 30 ml/min/1.73m^2. The adverse-event record lists 10 participants at risk in Group A, 10 in Group B, and 9 in Group C. These are safety denominators, not a reported accounting of every analysis population.
Each group received tolvaptan for the first 3 weeks of the 6 week study. The dose was increased weekly through 45/15 mg, 60/30 mg, and 90/30 mg split doses, subject to the maximally tolerated dose. The listed schedule was AM and PM, with the second dose 8 hours later. The design therefore included a treatment period and a period after treatment, but no parallel untreated comparison is described.
Because allocation was not randomized and all groups received tolvaptan, differences among the eGFR groups cannot be interpreted as randomized treatment effects. They may describe responses within distinct renal-function categories, but the registry record does not report numerical primary endpoint results or enough analysis details to assess the estimated changes. The method used to assign individuals to the groups beyond eGFR category is 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: The trial consisted of a 2- to 42-day screening period, a 3-week treatment period, and a 3-week post treatment period.
Overall Study
| Stage | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 ml/Min/1.73m2 |
|---|---|---|---|
| STARTED | 10 | 10 | 9 |
| COMPLETED | 9 | 9 | 9 |
| NOT COMPLETED | 1 | 1 | 0 |
Reasons for not completing this period:
| Reason | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 ml/Min/1.73m2 |
|---|---|---|---|
| Adverse Event | 1 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants who took any trial medication and had a postbaseline renal function test.
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.
| Characteristic | Unit | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 | Total |
|---|---|---|---|---|---|
| Participants analysed | 10 | 10 | 9 | 29 | |
| Age, Continuous | Years | 38.7 (SD 7.1) | 47.8 (SD 12.9) | 52.1 (SD 6.7) | 46.0 (SD 10.7) |
| Sex: Female, Male: Female | Participants | 6 | 6 | 2 | 14 |
| Sex: Female, Male: Male | Participants | 4 | 4 | 7 | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Change From Baseline in Measured Glomerular Filtration Rate (mGFR) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment., measured over After 3 weeks of treatment and 3 weeks post treatment.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mL/min |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was mean change from baseline in measured glomerular filtration rate (mGFR), measured after 3 weeks of tolvaptan treatment and at 3 weeks post treatment. The measure is reported in mL/min, with the mean and standard deviation specified as the summary statistics. mGFR is a direct renal-function measurement in this study, rather than an eGFR category used to define the groups.
Renal function measurements used a constant infusion method with 125I-iothalamate and 131I-hippuran. Following a priming solution at 08:00 hours, a constant infusion was administered, with the lowest infusion rates used for participants with impaired renal function according to previously known serum creatinine concentrations. After a 1.5-hour equilibration, simultaneous clearances of the tracers were measured over two 2-hour periods. Blood was drawn at 1, 2, 3, 4, and 5 hours after water/tolvaptan consumption at 08:30 hours. The mGFR measurement was corrected for voiding errors.
In general, measuring mGFR can provide a renal-function endpoint that is less dependent on an estimated value alone. Assessing it during treatment and after treatment ended can describe whether measurements differed across those time points. That design does not, by itself, establish why any difference occurred or whether it was caused by tolvaptan. Numerical endpoint estimates, standard deviations, and confidence intervals are not reported in the registry record, so the size and precision of the changes cannot be evaluated from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary measure and its assessment times, but it does not report numerical results for mean change from baseline in mGFR. It therefore does not establish the magnitude or direction of the observed changes after 3 weeks of treatment or at 3 weeks post treatment. The absence of numerical estimates in the record is not evidence that the change was zero, or that no change occurred. It means that this outcome cannot be quantitatively interpreted from the registry record.
No confidence interval, standard error, p-value, or group-specific primary endpoint estimate is reported in the registry record. Without these, readers cannot assess statistical uncertainty, distinguish a precise estimate from a highly variable one, or judge how compatible the data are with different possible changes. A mean and standard deviation are named as the endpoint’s summary approach, but the corresponding values are not reported.
The three eGFR categories are clinically and statistically distinct groups, not randomized treatment arms. All received tolvaptan. Any comparison among those categories would combine differences in baseline renal function with other potential between-group differences. In general, non-randomized group comparisons can be affected by confounding, and this design does not provide a concurrent untreated group to separate treatment-period changes from other changes over time.
The record describes additional outcomes involving free water clearance, pharmacokinetic measures, total kidney volume, and urine volume. It lists 10 outcome measures and 63 analyses, but does not provide numerical results for the primary endpoint in the record represented by these registry entries. The number of analyses alone does not reveal which comparisons were prespecified, how they were adjusted, or how many were statistically significant. Those details are not reported in the registry record.
The safety record reports serious adverse events affecting 1 participant in the eGFR > 60 group, 0 in the eGFR 30-60 group, and 1 in the eGFR <30 group. These counts describe observed safety events in this study; they do not resolve the missing primary efficacy estimates. As the study had no control group and the record does not report primary endpoint estimates, the statistical interpretation must remain descriptive rather than a comparison of treatment against no treatment.
Overall, the design and endpoint are identifiable, but the main quantitative result is not. No conclusion about the size, precision, or statistical significance of the mGFR change can be drawn from the registry record. That uncertainty should not be replaced with an assumption of benefit, lack of benefit, or equivalence.
9. Statistical Methods Explained
What does a mean change describe?
The primary outcome is a continuous measure, and its specified summary is a mean change from baseline. In general, a mean change combines individual changes into one average value. That average describes the center of the observed changes, but it does not show how widely individual results varied. The registry names standard deviation as the measure of dispersion. In general, standard deviation describes variation among observations around their mean; it is not a confidence interval and does not directly communicate the precision of the mean.
The record specifies measurements after 3 weeks of treatment and at 3 weeks post treatment. Those are distinct assessment times, and a change at one time cannot be assumed to match a change at the other. No numerical mean changes or standard deviations are reported in the registry record, so neither the average pattern nor the variability can be described numerically.
What would a confidence interval add?
In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater statistical precision than a wider interval, while the interval’s location indicates which values remain compatible with the data and method. It is not a guarantee that the true value lies within a particular interval, and it does not substitute for considering design limitations. No confidence interval for the primary outcome is reported in the registry record.
Likewise, a p-value would address compatibility between data and a specified null hypothesis under an analysis model; it would not measure the size or importance of an effect. The registry record does not report a primary-outcome p-value or an analysis model for that endpoint. Statistical significance therefore cannot be assessed from the available record.
Why does the non-randomized structure matter?
In general, randomization helps balance measured and unmeasured prognostic factors between treatment groups. Here, allocation is listed as non-randomized, and the groups are defined by eGFR category. Since all three groups received tolvaptan, the eGFR categories do not provide a treatment-versus-control contrast. Differences among categories may reflect renal-function differences or other group characteristics, rather than a treatment effect.
Repeated measurements before, during, and after exposure can describe temporal patterns. But a before-and-after comparison alone cannot rule out other explanations for a change, such as measurement variability, concurrent events, or natural fluctuation. Those possibilities are general considerations; the record does not report whether or how they were addressed in the analysis.
How should the planning illustrations be read?
The registry’s sample-size assumptions describe planning illustrations based on the observed effect, not the trial’s own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event calculations, the stated quantity is total events; for other calculations, it is participants per arm. The numerical planning outputs and fractions are not reported in the registry record represented by these registry entries.
In general, a sample-size calculation estimates how many observations a hypothetical study might need under specified assumptions. Such an illustration is not observed power, and it does not show the probability that the completed study detected an effect. In this case, an equal-allocation, two-arm illustration also does not mirror the non-randomized study with three eGFR categories and no control arm. These illustrations should be understood as conditional planning scenarios, not as an analysis of the completed trial’s strength or success.
What does over-dispersion mean in general?
For count outcomes, over-dispersion means the observed variability exceeds what a chosen model assumes. In general, ignoring excess variability can make uncertainty look smaller than it is. This is a general statistical concept; the primary mGFR outcome is continuous, and the registry record does not identify an over-dispersion model for this trial. The record also does not describe the statistical models used for the secondary outcomes.
For this continuous endpoint, the key missing elements are the estimates, their variability, and a description of the inferential method. The registry gives the measurement procedures and names the mean and standard deviation, but does not report the numerical primary results or the model used to analyze them. It is therefore possible to explain what the endpoint was intended to measure, but not to reconstruct its statistical result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 outcome measures and 63 analyses. The listed outcomes cover mGFR and secondary measures that include free water clearance, time to peak plasma concentration, area under the concentration-time curve, total kidney volume, and urine volumes. Multiple outcomes, time points, groups, or analyses can create multiplicity: in general, the more statistical comparisons made, the greater the chance that some results may appear notable by chance if no adjustment or prespecified hierarchy is used.
The registry record does not report whether a multiplicity adjustment was planned or applied, which outcomes were designated for confirmatory inference, or how the 63 analyses were organized. It does not report an interim-analysis plan or a statistical analysis plan. Those details should not be inferred from the number of analyses or from the endpoint list.
The primary endpoint population is defined as participants who took any trial medication and had a postbaseline renal-function test. The number included in that analysis is not reported in the registry record. The record does not describe missing-data handling, reasons for missing measurements, imputation, sensitivity analyses, or whether any other analysis populations were used. It is therefore not possible to determine whether the primary endpoint analysis included every enrolled participant or how missing measurements may have affected the results.
In general, analysis-population definitions and missing-data methods matter because excluding participants or measurements can alter the population represented by an estimate. Here, the stated primary population is available, but the details needed to evaluate missingness and its handling are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| eGFR > 60 mL/Min/1.73m2 | 1 | 10 | 10.0% |
| eGFR 30-60 mL/Min/1.73m2 | 0 | 10 | 0.0% |
| eGFR <30 mL/Min/1.73m2 | 1 | 9 | 11.1% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| eGFR > 60 mL/Min/1.73m2 | 10 of 10 |
| eGFR 30-60 mL/Min/1.73m2 | 10 of 10 |
| eGFR <30 mL/Min/1.73m2 | 9 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|---|
| Polyuria | Renal and urinary disorders | 1 of 10 | 0 of 10 | 0 of 9 |
| Angina pectoris | Cardiac disorders | 0 of 10 | 0 of 10 | 1 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|---|
| Thirst | General disorders | 10 of 10 | 10 of 10 | 8 of 9 |
| Polyuria | Renal and urinary disorders | 9 of 10 | 9 of 10 | 7 of 9 |
| Nocturia | Renal and urinary disorders | 8 of 10 | 6 of 10 | 6 of 9 |
| Dry mouth | Gastrointestinal disorders | 6 of 10 | 5 of 10 | 5 of 9 |
| Decreased appetite | Metabolism and nutrition disorders | 2 of 10 | 3 of 10 | 2 of 9 |
| Fatigue | General disorders | 2 of 10 | 1 of 10 | 3 of 9 |
| Headache | Nervous system disorders | 2 of 10 | 2 of 10 | 2 of 9 |
| Nausea | Gastrointestinal disorders | 1 of 10 | 1 of 10 | 2 of 9 |
| Dizziness | Nervous system disorders | 1 of 10 | 2 of 10 | 1 of 9 |
| Renal pain | Renal and urinary disorders | 3 of 10 | 0 of 10 | 1 of 9 |
Serious events with the highest arm-level rate: angina pectoris (11.1%), polyuria (10.0%).
The safety record divides participants by eGFR group. In the eGFR > 60 mL/Min/1.73m2 group, 10 were at risk for serious adverse events and 1 was affected. In the eGFR 30-60 mL/Min/1.73m2 group, 10 were at risk and 0 were affected. In the eGFR <30 mL/Min/1.73m2 group, 9 were at risk and 1 was affected. These are counts recorded for the groups, not comparative estimates of risk.
For other, non-serious adverse events, the record lists 10 affected among 10 at risk in each of the first two groups, and 9 affected among 9 at risk in the third. The registry also lists Angina pectoris at 11.1% and Polyuria at 10.0% among the top serious terms. The denominators for these percentages are not reported in the registry record, so they should not be converted into participant counts.
The death counts are not reported in the registry record. These safety counts are descriptive, and the study has no untreated comparator. Small group counts and the absence of a control group limit what can be inferred about comparative safety. The figures do not establish whether an event was caused by tolvaptan.
12. What the Result Does, and Does Not, Mean
This trial’s registry description identifies a short-term study of oral tolvaptan in ADPKD across three eGFR categories. It specifies a primary renal-function endpoint, measurement procedures, treatment timing, and a post-treatment assessment. These details show what the investigators set out to measure and how the measurement was obtained. They do not provide the numerical primary results needed to characterize the observed mGFR changes.
The record does not report the mean change, standard deviation, confidence interval, or p-value for the primary outcome. Consequently, it cannot support a numerical statement about the direction, size, variability, or statistical significance of mGFR change. The missing estimates do not mean that the effect was zero or that the study found no change; they mean that the outcome cannot be evaluated quantitatively from the registry record.
The study also cannot establish a randomized treatment effect. Allocation was non-randomized, all groups received tolvaptan, and the groups were based on renal-function category. A comparison among groups would not be the same as comparing tolvaptan with an untreated or placebo group. In general, differences between these categories may reflect differences in participants as well as any difference in response.
The safety record reports serious-event counts by eGFR category and selected serious-event terms, but does not provide a control group for comparison. These figures describe events observed in the enrolled groups; they do not establish causation or a comparative safety rate. The listed secondary outcomes broaden the study’s measurements, but their numerical results and analysis details are not reported in the registry record.
The reasonable interpretation is therefore bounded: this is a completed, non-randomized, unmasked Phase 2a investigation of short-term renal hemodynamic effects, with a defined mGFR endpoint and descriptive safety information. The registry record does not provide enough numerical outcome information to judge the magnitude or precision of the primary result, and it does not support claims of treatment efficacy or lack of efficacy.
13. Why This Trial Matters Statistically
This study is statistically notable for the combination of a physiological measurement and a short treatment-and-follow-up schedule. The primary endpoint was measured mGFR, obtained using tracer clearances and a constant infusion method, rather than relying only on the eGFR categories used to define groups. The endpoint description is detailed enough to identify the intended measurement process and the assessment times.
The design also illustrates why a clear endpoint does not guarantee an interpretable treatment comparison. The study was non-randomized, unmasked, and parallel, with groups defined by baseline renal-function category. Each group received tolvaptan, and no control arm is described. The design can organize short-term observations across different levels of renal function, but it does not create a randomized contrast between treatment and no treatment.
Another statistical issue is the distance between a registry’s design information and its numerical results. The record identifies 10 outcome measures and 63 analyses, but does not report the primary mGFR estimates or the methods needed to interpret uncertainty and multiplicity. This makes it important to distinguish a clearly specified measurement from a fully assessable result. The recorded method can be understood even when the outcome magnitude cannot.
The study’s safety counts also illustrate the limits of small descriptive groups. The record lists 10, 10, and 9 participants at risk across the three eGFR categories, with serious adverse events affecting 1, 0, and 1, respectively. Without a control group, these counts are not comparative evidence about treatment-related risk.
Overall, the study matters as an example of short-term physiological assessment across renal-function strata and as a reminder that design, endpoint definition, and reporting of estimates all shape statistical interpretation. Its registry record describes the first two in detail, but leaves the primary outcome’s numerical size and precision unreported.
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.
A central limitation is that numerical primary endpoint results are not reported in the registry record. The mean changes in mGFR, standard deviations, and any inferential results are unavailable, preventing an assessment of direction, magnitude, variability, or precision. The same limitation applies to the secondary outcomes listed in the record: their numerical findings are not included in the registry record.
The study was non-randomized and had no described untreated or placebo comparison group. All eGFR categories received tolvaptan, so observed changes over time cannot be separated from other possible time-related or measurement-related explanations using a concurrent control. Differences across categories also cannot be treated as randomized treatment contrasts.
The study was unmasked. The registry record does not report whether outcome assessment or analysis was blinded, and that information should not be assumed. The record also does not describe the method used to assign participants to eGFR groups beyond the categories themselves, or report baseline characteristics that could help assess comparability across groups.
Although the primary analysis population is defined, its size is not reported. Missing-data methods, reasons for missing follow-up measurements, and sensitivity analyses are not reported in the registry record. Nor are the statistical analysis model, multiplicity procedures, interim analyses, or sample-size justification. The sample-size assumptions describe planning illustrations rather than the trial’s own design; numerical illustration outputs are not reported.
Finally, safety counts are descriptive and based on small group denominators, without an untreated comparator. The percentages listed for serious-event terms have no denominator reported in the registry record, and death counts are not reported. These reporting and design limitations constrain both efficacy interpretation and comparative safety conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Short-term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD) — NCT01336972.
- Registry record last updated 2019-03-05; status last verified 2019-02.
- Results first posted 2017-06-28.
- 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.
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18. Record Summary
NCT01336972 is a completed, single-center Phase 2a, non-randomized, unmasked, parallel study of oral tolvaptan in participants with ADPKD. Enrollment was 29. Participants were grouped by eGFR category and received tolvaptan during the first 3 weeks of a 6 week study, with weekly dose titration up to the maximally tolerated dose.
The primary endpoint was mean change from baseline in measured GFR after 3 weeks of treatment and at 3 weeks post treatment. The record describes tracer-clearance measurement procedures and defines the primary population as participants who took any trial medication and had a postbaseline renal-function test. Numerical primary endpoint estimates and measures of uncertainty are not reported in the registry record.
Safety information is listed by eGFR group, including serious adverse-event counts and selected serious-event terms. The non-randomized design has no described control group, and the record does not report the statistical analysis plan, missing-data methods, or multiplicity approach.