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 Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease) (NCT02964273), a randomized phase 3 study. The primary outcome is Phase A: Change From Baseline in Spot Urine Osmolality (Pre-morning Dose).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02964273 |
| Phase | Phase 3 |
| Condition | Autosomal Dominant Polycystic Kidney Disease (ADPKD) |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 91 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Otsuka Pharmaceutical Development & Commercialization, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Children and adolescents with autosomal dominant polycystic kidney disease (ADPKD). The registry record lists an enrollment of 91. The primary analysis population is described as participants who were randomized, received at least one dose of investigational medicinal product, and had both a Phase A baseline and at least one postbaseline efficacy evaluation.
Intervention
Oral tolvaptan, given as a split dose in Phase A. The study also included a two-year open-label extension in which qualified participants could continue or begin tolvaptan, depending on their Phase A assignment.
Comparator
Matching placebo in Phase A, given orally as a split dose. The randomized comparison was double-blind and placebo-controlled; participants who entered the open-label extension received tolvaptan.
Primary question
How did spot urine osmolality, measured before the morning dose, change from baseline to Week 1 of Phase A? The registry describes this endpoint but does not report a single numerical comparison of the change between the randomized groups.
The registry record frames the study’s primary objective as assessing long-term safety in children and adolescents with ADPKD. Its secondary objectives concern pharmacodynamics, pharmacokinetics, and efficacy. The primary endpoint listed for the posted results is a short-term measure of urine concentration, rather than a direct measure of kidney function or kidney volume. Those broader outcomes appear among the secondary measures, including estimated glomerular filtration rate and height-adjusted total kidney volume.
The randomized placebo-controlled period and the open-label extension address different questions. In Phase A, the treatment groups can be compared under randomized assignment. In Phase B, participants with prior placebo were offered tolvaptan, so the original randomized contrast is no longer maintained for that treatment period. The posted record does not give a single primary endpoint result that would answer the randomized comparison directly.
3. Trial Design
This was a Phase 3, randomized, parallel-group, multicenter study with triple masking. The official study title describes a one-year, double-blind, placebo-controlled randomized trial followed by a two-year open-label extension. The registry status is completed, and its recorded enrollment is 91. The sponsor is Otsuka Pharmaceutical Development & Commercialization, Inc.
During Phase A, participants were assigned to tolvaptan or matching placebo. Both were administered orally as split doses, with the first dose upon awakening and the second approximately eight hours later. Starting doses were based on weight. The full dose specifications are not reported in the registry record, so they are not reconstructed.
Phase B was an open-label extension. Qualified participants who had received tolvaptan in Phase A could continue, and qualified participants who had received placebo in Phase A could receive tolvaptan. Qualification is described in the registry record as requiring willingness to continue and absence of adverse events that would require discontinuation of the investigational medicinal product. The record does not provide a single randomized placebo comparison for the extension.
The study started on 2016-09-23, and the primary completion date is recorded as 2021-11-17. The primary endpoint was spot urine osmolality before the morning dose, assessed at baseline and Week 1 of Phase A. Other listed outcomes include kidney volume by MRI, renal function estimated with the Schwartz formula, fluid intake, urine volume, and fluid balance. The record lists 22 outcome measures, but no analyses are recorded for the posted results. Details such as the randomization ratio and the full statistical analysis plan 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 91 participants with autosomal dominant polycystic kidney disease (ADPKD) were randomized into 2 groups in a 1:1 ratio to receive tolvaptan or matching placebo.
Phase A: Double-blind Period (12 Months)
| Stage | Phase A: Tolvaptan | Phase A: Placebo | Phase B: Prior Tolvaptan | Phase B: Prior Placebo |
|---|---|---|---|---|
| STARTED | 48 | 43 | 0 | 0 |
| Dense Pharmacokinetic/Pharmacodynamic (PK/PD) Population | 12 | 8 | 0 | 0 |
| COMPLETED | 44 | 40 | 0 | 0 |
| NOT COMPLETED | 4 | 3 | 0 | 0 |
Reasons for not completing this period:
| Reason | Phase A: Tolvaptan | Phase A: Placebo | Phase B: Prior Tolvaptan | Phase B: Prior Placebo |
|---|---|---|---|---|
| Adverse Events | 1 | 0 | 0 | 0 |
| Physician Decision | 0 | 2 | 0 | 0 |
| Withdrawal by Subject | 3 | 1 | 0 | 0 |
Phase B: Open-label Period (24 Months)
| Stage | Phase A: Tolvaptan | Phase A: Placebo | Phase B: Prior Tolvaptan | Phase B: Prior Placebo |
|---|---|---|---|---|
| STARTED | 0 | 0 | 42 | 39 |
| COMPLETED | 0 | 0 | 36 | 33 |
| NOT COMPLETED | 0 | 0 | 6 | 6 |
Reasons for not completing this period:
| Reason | Phase A: Tolvaptan | Phase A: Placebo | Phase B: Prior Tolvaptan | Phase B: Prior Placebo |
|---|---|---|---|---|
| Adverse Events | 0 | 0 | 0 | 2 |
| Withdrawal by Subject | 0 | 0 | 4 | 3 |
| Reason Not Specified | 0 | 0 | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) included all participants who were randomized to a treatment group, received at least 1 dose of the investigational medicinal product (IMP), and had both a Phase A baseline and at least 1 postbaseline efficacy evaluation. Number analyzed is the number of participants with data available for analysis at the given time point.
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: The Randomized Sample included all participants who were randomized in the trial.
| Characteristic | Unit | Phase A: Tolvaptan | Phase A: Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 48 | 43 | 91 | |
| Age, Continuous | years | 12.9 (SD 3.2) | 12.8 (SD 2.8) | 12.9 (SD 3.0) |
| Sex: Female, Male: Female | Participants | 21 | 23 | 44 |
| Sex: Female, Male: Male | Participants | 27 | 20 | 47 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 1 | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 47 | 42 | 89 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 46 | 42 | 88 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Phase A: Change From Baseline in Spot Urine Osmolality (Pre-morning Dose), measured over Baseline, and Week 1 of Phase A.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | milliosmoles per kilogram (mOsm/kg) |
| Endpoint classification | Continuous Endpoint |
Spot urine osmolality measures how concentrated a urine sample is. It is reported in milliosmoles per kilogram of water and measured with an osmometer, using the freezing-point depression of a solution. The trial collected a spot sample immediately before the morning dose at baseline on Day 1 and again at Week 1 of Phase A. The collection description specifies a sample after the first morning void, collected as a mid-stream, clean-catch specimen; participants were fasting.
The endpoint is the change from baseline in the mean spot urine osmolality. A change score expresses how the measured value at follow-up differs from the participant’s baseline value; the group-level mean summarizes those changes. The registry identifies standard deviation as the measure of dispersion. Standard deviation describes the spread of participant-level measurements around the mean, rather than the uncertainty in the estimated group mean.
Urine osmolality is used as a measure of urine concentration. That makes it a pharmacodynamic measure: it can describe a biological response associated with treatment. It is not, by itself, a direct measurement of kidney function, kidney structure, or a long-term clinical outcome. The registry also lists renal-function and kidney-volume outcomes separately.
No single numerical estimate of the primary endpoint change, group contrast, confidence interval, or test result is reported in the registry record. Therefore, the magnitude, direction, and precision of the primary result cannot be described from the posted primary-outcome information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary endpoint is defined as change in spot urine osmolality from baseline to Week 1 of Phase A, with results characterized using a mean and standard deviation. However, the registry record does not report a single numerical primary-outcome comparison. It therefore does not establish from the posted results how large the mean change was in either randomized group, whether the groups differed, or how precisely any difference was estimated.
This absence matters for interpretation. A treatment-group mean change alone would describe change within that group; it would not, on its own, show how change compared with placebo. A randomized between-group contrast is generally the relevant estimate for assessing the difference associated with assignment during the blinded Phase A period. No such estimate, confidence interval, or p-value is reported for this primary outcome. The record also does not provide participant-level outcome counts or the number analyzed for this result.
The registry identifies additional outcomes, including height-adjusted total kidney volume by MRI, estimated glomerular filtration rate, and measures of fluid balance. These outcomes provide different kinds of information. For example, an osmolality measure concerns urine concentration, whereas estimated glomerular filtration rate is a renal-function measure and kidney volume is an imaging measure. The presence of these outcomes in the registry does not supply their results: no outcome analyses are recorded in the posted results.
The safety counts describe serious adverse events in Phase A and in the extension groups identified by prior treatment. They are not a substitute for the primary efficacy comparison. In Phase A, the reported serious-event counts were 1 among 48 at risk in the tolvaptan group and 6 among 43 at risk in the placebo group. In Phase B, the counts were 7 among 42 at risk in the prior-tolvaptan group and 8 among 39 at risk in the prior-placebo group. These are descriptive counts, not adjusted comparisons. Phase B is open-label and includes participants grouped by prior assignment, so its counts should not be read as a continuation of the original randomized placebo contrast.
The registry record does not report the duration each participant was observed for safety, methods for handling incomplete follow-up, or a statistical comparison for these event counts. Without those details and without inferential estimates, the counts alone do not establish a causal difference in risk between groups. The record also reports no deaths in any listed group.
Overall, the posted record identifies a trial design, endpoint definitions, and safety counts, but does not provide the statistical results needed to quantify the primary treatment contrast. This interpretation is limited to what is reported in the registry record; it does not infer results from the study title, objectives, or outcome list.
9. Statistical Methods Explained
What does a change-from-baseline mean describe?
A change score is calculated for each participant by comparing a follow-up measurement with that participant’s baseline measurement. The group mean change summarizes those individual changes. For a continuous measure such as urine osmolality, the standard deviation describes how spread out the individual measurements or changes are around the mean. It is not the same as a confidence interval: a standard deviation describes variability among observations, while a confidence interval describes uncertainty around an estimated quantity.
In general, a randomized trial’s treatment effect for a continuous endpoint is often expressed as a difference between group means, with an interval estimate to show precision. The registry record does not report a single such comparison for this primary endpoint. It also does not report a confidence interval, p-value, or a numerical group mean change in the posted primary results. No effect size or precision estimate should therefore be inferred.
Why distinguish a within-group change from a between-group contrast?
A group’s mean may change over time for reasons that apply whether or not participants received the study treatment. A placebo group helps provide a contemporaneous reference during the randomized period. Comparing change between randomized groups can account for changes that occur in both groups, subject to the assumptions and conduct of the trial. A change observed in one group alone is not the randomized treatment contrast. This is general statistical context; the registry record does not report the primary between-group estimate needed to apply that interpretation to this trial.
What do mean and standard deviation contribute?
The mean gives a measure of the center of a continuous outcome, while the standard deviation describes participant-to-participant spread. A mean can be informative about the average response but does not show whether individual responses were similar. A standard deviation can help describe that heterogeneity, but neither quantity alone gives the uncertainty of a treatment contrast. The registry lists the primary parameter as a mean and the dispersion measure as standard deviation. It does not report the numerical values needed to assess the observed mean, spread, or precision.
What can be inferred from the trial’s design?
Random allocation supports a comparison of the assigned groups during Phase A, while masking is intended to limit influence from knowledge of treatment assignment. The registry lists the allocation as randomized, the model as parallel, and masking as triple. These design labels do not reveal whether the groups were balanced on measured characteristics, whether masking was maintained, or what analysis model was used. Those details are not reported in the registry record.
The extension has a different inferential structure. Participants who entered Phase B had to meet qualification conditions, and participants who had previously received placebo then received tolvaptan. Because there was no concurrent placebo group in the open-label extension as described, Phase B does not preserve the original randomized comparison for the treatment period. Comparisons by prior-treatment group can be affected by selection into the extension and by the differing treatment histories. The record does not report methods designed to address those issues.
How should the safety counts be read?
“At risk” indicates the group denominator used for the reported safety event count. A serious adverse event count is a number of participants with such an event, not a rate per unit of follow-up time. In general, event counts do not account for unequal exposure duration unless a rate analysis is reported. The registry lists counts and at-risk denominators but does not report exposure-adjusted rates or inferential comparisons. The serious-event figures should therefore be read descriptively, not as a statistical test of group differences.
What is the role of a planning illustration?
General sample-size calculations ask how many participants per arm might be needed under stated assumptions to detect a chosen effect with a specified power and significance level. Such calculations depend on assumptions about the effect, variability, allocation, and statistical method. The registry record describes planning illustrations based on fractions of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. These are planning illustrations, not observed power, and they are not evidence that the trial was designed around those assumptions. A trial’s own sample-size justification is not reported in the registry record. No numerical sample-size illustration or observed primary effect is stated in the record summarized for this analysis.
General statistical caution also applies when outcomes are over-dispersed: if variability is greater than a model assumes, standard errors and confidence intervals can be too optimistic unless the analysis accounts for that extra variation. This is a general point, not a claim about this trial. The registry record does not report an over-dispersion assessment or a model for the primary endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 22 outcome measures, including the primary urine-osmolality measure and secondary outcomes relating to kidney volume, renal function, and fluid measures. When a study examines multiple outcomes, time points, or comparisons, the chance of at least one apparently unusual result can increase if each is interpreted as a separate test. Statistical plans may address this multiplicity through a prespecified hierarchy or adjustment. The multiplicity strategy for this trial is not reported in the registry record.
The primary outcome information is not presented as a single comparison: the posted primary outcome has several categories or time points and is not reduced to one comparison. No analysis is recorded for the primary outcome in the results, and the registry lists zero analyses. Consequently, there is no reported primary estimate or inferential result to interpret alongside any multiplicity procedure. Whether a particular endpoint or time point was designated as the principal confirmatory test beyond the stated primary outcome is not reported in the registry record.
The Full Analysis Set is described as including participants randomized to a treatment group who received at least one dose of investigational medicinal product and had both a Phase A baseline and at least one postbaseline efficacy evaluation. This definition excludes randomized participants who did not meet those conditions. The number analyzed for the primary endpoint is not reported in the registry record. The record does not explain how missing Week 1 measurements were handled, whether any imputation was used, or how participants with incomplete follow-up were treated in the analysis.
General statistical context: excluding participants with missing outcomes can produce bias if the reasons for missingness are related to treatment or outcome. Methods for missing data depend on assumptions about why observations are missing; the choice of method and its assumptions should be reported to support interpretation. No missing-data method or sensitivity analysis is reported in the registry record. The randomization allocation ratio and detailed analysis populations for the secondary outcomes are also not reported.
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 |
|---|---|---|---|
| Phase A: Tolvaptan | 1 | 48 | 2.1% |
| Phase A: Placebo | 6 | 43 | 14.0% |
| Phase B: Prior Tolvaptan | 7 | 42 | 16.7% |
| Phase B: Prior Placebo | 8 | 39 | 20.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Phase A: Tolvaptan | 0 of 48 |
| Phase A: Placebo | 0 of 43 |
| Phase B: Prior Tolvaptan | 0 of 42 |
| Phase B: Prior Placebo | 0 of 39 |
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 |
|---|---|
| Phase A: Tolvaptan | 45 of 48 |
| Phase A: Placebo | 42 of 43 |
| Phase B: Prior Tolvaptan | 38 of 42 |
| Phase B: Prior Placebo | 39 of 39 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase A: Tolvaptan | Phase A: Placebo | Phase B: Prior Tolvaptan | Phase B: Prior Placebo |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 0 of 48 | 0 of 43 | 1 of 42 | 1 of 39 |
| COVID-19 | Infections and infestations | 0 of 48 | 0 of 43 | 2 of 42 | 0 of 39 |
| Alanine aminotransferase increased | Investigations | 0 of 48 | 0 of 43 | 1 of 42 | 1 of 39 |
| Aspartate aminotransferase increased | Investigations | 0 of 48 | 0 of 43 | 0 of 42 | 2 of 39 |
| SARS-COV-2 test positive | Investigations | 0 of 48 | 0 of 43 | 1 of 42 | 1 of 39 |
| Renal impairment | Renal and urinary disorders | 0 of 48 | 0 of 43 | 1 of 42 | 1 of 39 |
| Viral pericarditis | Infections and infestations | 1 of 48 | 0 of 43 | 0 of 42 | 0 of 39 |
| Hand fracture | Injury, poisoning and procedural complications | 0 of 48 | 1 of 43 | 0 of 42 | 0 of 39 |
| Intentional overdose | Injury, poisoning and procedural complications | 0 of 48 | 1 of 43 | 0 of 42 | 0 of 39 |
| Ulna fracture | Injury, poisoning and procedural complications | 0 of 48 | 1 of 43 | 0 of 42 | 0 of 39 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase A: Tolvaptan | Phase A: Placebo | Phase B: Prior Tolvaptan | Phase B: Prior Placebo |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | 16 of 48 | 21 of 43 | 15 of 42 | 17 of 39 |
| Nasopharyngitis | Infections and infestations | 10 of 48 | 14 of 43 | 11 of 42 | 13 of 39 |
| Polyuria | Renal and urinary disorders | 13 of 48 | 2 of 43 | 2 of 42 | 13 of 39 |
| Vomiting | Gastrointestinal disorders | 7 of 48 | 10 of 43 | 5 of 42 | 7 of 39 |
| Cough | Respiratory, thoracic and mediastinal disorders | 7 of 48 | 5 of 43 | 7 of 42 | 8 of 39 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 4 of 48 | 6 of 43 | 9 of 42 | 7 of 39 |
| Abdominal pain | Gastrointestinal disorders | 6 of 48 | 3 of 43 | 4 of 42 | 12 of 39 |
| Blood creatinine increased | Investigations | 9 of 48 | 2 of 43 | 7 of 42 | 5 of 39 |
| Nausea | Gastrointestinal disorders | 3 of 48 | 7 of 43 | 7 of 42 | 5 of 39 |
| Pyrexia | General disorders | 4 of 48 | 3 of 43 | 8 of 42 | 7 of 39 |
Serious events with the highest arm-level rate: aspartate aminotransferase increased (5.1%), covid-19 (4.8%), abdominal pain (2.6%), arthritis bacterial (2.6%), expired product administered (2.6%).
Serious adverse events are reported separately for Phase A and Phase B. In Phase A, the registry records 1 serious event among 48 at risk in the tolvaptan group and 6 among 43 at risk in the placebo group. In Phase B, it records 7 among 42 at risk in the group with prior tolvaptan and 8 among 39 in the group with prior placebo. The registry reports zero deaths in each listed group.
These are counts of participants affected, not estimates adjusted for length of exposure. The record does not report exposure-adjusted rates, confidence intervals, or a statistical test comparing the groups. The counts can describe what was recorded in each group, but do not by themselves establish that treatment caused a difference in serious-event risk. The Phase B labels refer to prior Phase A treatment, while both extension groups received tolvaptan; Phase B is therefore not a placebo-controlled comparison.
The registry also lists serious-event terms with percentages: Aspartate aminotransferase increased, 5.1%; COVID-19, 4.8%; Abdominal pain, 2.6%; Arthritis bacterial, 2.6%; Expired product administered, 2.6%; and Alanine aminotransferase increased, 2.6%. The record does not give the denominator or further analysis details alongside these terms in the information. These percentages should be read as registry listings, not as evidence of comparative risk or causation.
12. What the Result Does, and Does Not, Mean
The registry record documents a randomized, masked, placebo-controlled Phase A study of tolvaptan in children and adolescents with ADPKD, with a later open-label extension. It specifies a primary endpoint based on change in spot urine osmolality from baseline to Week 1. That definition clarifies what was intended to be measured, but the posted results do not provide a single numerical comparison for the endpoint. The direction and size of any randomized-group difference, and its precision, therefore cannot be stated.
The record also names outcomes concerning kidney volume, renal function, and fluid measures. Their inclusion indicates the range of outcomes assessed or planned, not their results. The registry lists 22 outcome measures and zero analyses. In the absence of posted outcome analyses, no claim about a treatment effect on those measures can be drawn from the outcome list alone.
The safety results give descriptive serious adverse event counts for the randomized period and the open-label extension, along with zero deaths in each listed group. Those figures provide a record of events as reported, but are not exposure-adjusted comparisons and do not establish causation. The extension’s participants were selected for continued participation under stated eligibility conditions, and Phase B was open label; these features further distinguish its counts from a randomized placebo comparison.
The record’s design and objectives should not be confused with evidence of benefit or harm. A Phase 3 designation, randomization, masking, and a completed status describe trial characteristics, not the direction or certainty of a result. The primary result, analysis methods, missing-data handling, and multiplicity approach are not reported in the registry record. As a result, the available information supports describing the study’s structure and reported safety counts, but not drawing a quantitative conclusion about the primary endpoint or broader efficacy outcomes.
13. Why This Trial Matters Statistically
This trial is statistically notable for the distinction between its randomized Phase A and its open-label extension. Randomization and masking support interpretation of a treatment comparison during the placebo-controlled period, while the extension addresses continued exposure in participants who qualified to remain. Because the extension was open label and participants with prior placebo received tolvaptan, its group labels describe treatment history rather than a continuing randomized placebo contrast.
The primary endpoint is a continuous pharmacodynamic measure collected at baseline and Week 1. This creates a clear measurement question—how urine concentration changed over the short interval—but it is not interchangeable with outcomes such as estimated glomerular filtration rate or kidney volume. The registry lists these outcomes separately, underscoring that a short-term biomarker and longer-term measures answer different statistical and clinical questions.
The record also illustrates why endpoint definitions and outcome results need to be considered separately. It defines the primary measure and its collection conditions, yet does not report a single primary comparison or any analyses. Without the estimated contrast and its uncertainty, the trial’s primary result cannot be quantified from the registry record. Safety counts can be described, but their interpretation also depends on follow-up and analysis details that are not reported.
For clinical researchers, these distinctions matter when assessing what a registry entry can support. Design information, outcome definitions, and adverse-event counts each contribute context, but they do not replace the prespecified statistical analysis and its estimates. The posted record is informative about the trial’s structure and measurement plan while leaving important inferential results unavailable.
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 statistical interpretation is that the registry record does not report a single numerical primary-outcome comparison. It also lists zero analyses, so no posted analysis estimate, uncertainty interval, or test result is available for the primary endpoint or the listed secondary outcomes. The record therefore cannot support a quantitative assessment of the treatment contrast from these results.
The primary outcome reporting is not reduced to one comparison because it has several categories or time points. The record does not clarify how those categories or time points relate to any planned primary hypothesis test. Details of the statistical analysis plan, multiplicity control, and the rationale for the trial’s sample size are not reported in the registry record. Planning illustrations based on an observed effect do not establish the trial’s original design assumptions or its achieved power.
The analysis population is defined in general terms, but the number analyzed for the endpoint is not reported. The record does not specify the missing-data method, sensitivity analyses, or the treatment of participants without a Week 1 measurement. It also does not report whether the primary analysis adjusted for baseline or other covariates, or the model used to estimate change.
For safety, the posted information gives serious adverse event counts and at-risk denominators, but not exposure-adjusted rates, confidence intervals, or comparative tests. The record does not report enough detail to assess differences in observation time. Phase B is open label and restricted to qualified participants, so its descriptive counts do not preserve the randomized comparison from Phase A. These limitations are specific to the information recorded and do not establish that analyses or details are absent from other study materials.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease) — NCT02964273.
- Registry record last updated 2023-01-03; status last verified 2022-12.
- Results first posted 2023-01-03.
- 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
NCT02964273 is a completed Phase 3 randomized parallel-group study of tolvaptan and matching placebo in children and adolescents with ADPKD. The official title describes a one-year double-blind, placebo-controlled period followed by a two-year open-label extension. The registry records an enrollment of 91, a start date of 2016-09-23, and a primary completion date of 2021-11-17.
The primary outcome is change from baseline in pre-morning-dose spot urine osmolality at Week 1 of Phase A. The registry describes the measurement and analysis population but does not report a single numerical primary comparison. It lists 22 outcome measures and zero analyses. Serious adverse event counts are recorded for both phases, with zero deaths in each listed group. Analysis methods for multiplicity and missing data are not reported in the registry record.