Phase 3 Safety and Efficacy Study of CTAP101 Extended-release Capsules in Children With Secondary Hyperparathyroidism: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 3 Safety and Efficacy Study of CTAP101 Extended-release Capsules in Children With Secondary Hyperparathyroidism (NCT05543928), a randomized phase 3 study. The primary outcome is Numbers of Subjects Who Attained Mean Decrease in Plasma iPTH of 30% From Baseline.

2. Clinical Question

In statistical terms, this is a planned responder comparison: each participant would be classified according to whether the specified biomarker decrease was attained, and the proportions in the two treatment groups would be compared. That approach differs from comparing average changes directly, because it focuses on meeting a threshold rather than the size of each participant’s change. The endpoint description gives the threshold and timeframe, but the posted results do not contain an estimate of either treatment-group proportion or their comparison. The study’s status and pre-randomization termination are therefore central to interpreting the question: the registry describes what the trial intended to evaluate, not a completed randomized test of that question.

3. Trial Design

The registry identifies this as a phase 3, multicenter study with randomized allocation, triple masking and a sequential model. Its brief summary describes a randomized, double-blind, placebo-controlled study, while the masking field lists triple masking. The record does not explain the difference between those descriptions. The planned interventions were CTAP101 extended-release capsules and placebo.

The record lists enrollment as 2 and gives the study status as terminated. The primary endpoint population description states that the study was terminated before randomization. Thus, the planned randomized comparison should not be mistaken for an observed randomized comparison. The enrollment figure alone does not establish how many participants received either intervention, and no treatment assignment is documented in the posted results.

The listed start date is 2023-01-31, and the listed primary completion date is 2024-06-19. These dates describe the record’s study timeline; they do not provide a reason for termination or show that the planned primary endpoint was measured. The reason for termination is not reported in the registry record.

The primary endpoint was specified as the number of subjects attaining a mean decrease in plasma iPTH of at least 30% from pretreatment baseline, with a timeframe of 26 weeks. The record also lists secondary outcomes relating to serum total 25-hydroxyvitamin D, plasma iPTH changes, pharmacodynamic effects and the incidence of hypercalcemia and hyperphosphatemia. It identifies seven outcome measures overall, but does not report an analysis for the primary or secondary outcomes. The registry record does not provide the protocol details needed to determine how the sequential model was implemented, how treatment was intended to be allocated, or what procedures governed the planned study conduct.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The study was terminated before randomization

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 study was terminated before randomization

6. Primary Endpoint

The registry lists the primary outcome as Numbers of Subjects Who Attained Mean Decrease in Plasma iPTH of 30% From Baseline, measured over 26 weeks.

The primary endpoint was the proportion of participants in the intent-to-treat population, ages 8 to <18 years, who attained a mean decrease in plasma iPTH of at least 30% from pretreatment baseline. The planned timeframe was 26 weeks, and the endpoint description states that the proportion would be compared with placebo during the EAP. The registry record does not expand EAP.

This is a threshold-based responder endpoint. In general, such an endpoint reduces a continuous measurement to a classification: a participant either meets the stated threshold or does not. A resulting group proportion can be easier to interpret as the frequency of meeting a defined response criterion than a mean change alone. However, the threshold classification does not retain all information about the size of each participant’s change. Two participants on opposite sides of the cutoff may have similar measurements, while participants who meet the cutoff may have different-sized decreases.

The endpoint is useful for a planned treatment comparison only if the relevant measurements and group assignments are available. The registry record says the study ended before randomization and reports no endpoint analysis. It therefore contains no observed responder proportions, treatment contrast, or estimate of the precision of that contrast. The endpoint definition explains what the trial intended to measure; it does not establish whether the endpoint was attained by any participant.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, masked, placebo-controlled design, but also states that the study was terminated before randomization. This distinction matters statistically. A design label describes the intended structure of a study; it does not establish that the random assignment or planned comparison took place. The posted results contain zero analyses, so there is no reported treatment-effect calculation to interpret.

What the responder endpoint represents

The primary endpoint defines a responder as a participant attaining a mean decrease in plasma iPTH of at least 30% from pretreatment baseline. The planned summary is a proportion: the number meeting the criterion relative to the relevant study population. In general, a comparison of proportions asks whether the observed frequency of meeting the criterion differs between groups. The endpoint description specifies comparison with placebo and gives a timeframe of 26 weeks, but no group proportions or contrast are reported in the registry record.

A threshold endpoint has a clear decision rule, but it compresses information. A participant just meeting the cutoff and a participant with a larger decrease both count as responders, while a participant just short of the cutoff counts as a non-responder. In general, the analysis can be sensitive to the choice of cutoff and to measurement variability near that cutoff. The registry record does not report the rationale for selecting this threshold or the measurement procedures used to assess the endpoint.

Randomization, masking and the intended comparison

Randomization is intended, in general, to make treatment groups comparable on average with respect to factors measured and unmeasured at baseline. Masking is intended to limit the influence of treatment knowledge on care, measurement or assessment. Those protections depend on the study actually implementing the planned procedures. Here, the record’s statement that termination occurred before randomization means that the planned randomized contrast cannot be treated as an observed comparison. The registry lists triple masking, while its brief summary calls the study double-blind; the record does not explain how those descriptions relate.

The record identifies CTAP101 capsules and placebo, but the arm descriptions contain no further details. The exact assignment procedures, masking roles, and intended analysis methods are not reported in the registry record. The sequential model is listed, but the record does not explain its implementation. No particular design or analysis procedure should be inferred from that label alone.

Precision and uncertainty

In general, an effect estimate describes the observed contrast between groups, while a confidence interval describes uncertainty around that estimate under specified assumptions. A narrow interval indicates greater statistical precision than a wide interval, although precision is not the same as clinical importance. Neither an estimate nor a confidence interval for the primary endpoint is reported in the registry record. As a result, readers cannot assess the direction, magnitude or precision of the planned comparison.

A p-value, when reported, describes how compatible the data are with a specified null hypothesis under an analysis model. It does not measure the probability that a treatment effect is true, and it does not describe effect size. No p-value or other hypothesis-test result for the primary endpoint is reported in the registry record. With no reported comparison, there is no basis for a statistical significance interpretation.

Over-dispersion and model choice

For general context, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model ignores over-dispersion, standard errors can be too small and uncertainty can appear understated. This issue can arise in some count or clustered-data analyses, but the registry record does not report a model for the primary endpoint, an over-dispersion assessment, or a finding of over-dispersion. It is therefore not possible to say that this issue affected the trial’s analysis.

The posted planning assumptions describe a general illustration using a two-sided significance level of 0.05, equal allocation, a normal approximation and fractions of an observed effect. Such planning illustrations are not observed power and are not evidence that a comparison was conducted. No numerical sample-size illustration for this endpoint is stated in the registry record, and the stated assumptions do not replace a trial-specific design justification. The trial’s own sample-size justification and statistical analysis plan are not reported in the registry record.

What can be inferred from the available analysis record

The registry identifies an intent-to-treat population in the primary endpoint description. In general, intention-to-treat analysis is tied to randomized assignment and aims to retain participants in their assigned groups for analysis. Since the record says the study ended before randomization and lists zero analyses, it does not provide an analyzed intent-to-treat comparison. It also does not report the number of participants with endpoint measurements, any treatment-group estimates, or uncertainty measures. The appropriate statistical reading is that the endpoint and intended design are specified, while the analysis needed to answer the treatment question is not reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures, including the primary responder endpoint and secondary measures relating to serum total 25-hydroxyvitamin D, plasma iPTH, pharmacodynamic effects, hypercalcemia and hyperphosphatemia. When a study assesses multiple outcomes or makes multiple comparisons, general statistical practice considers multiplicity: testing more hypotheses can increase the chance of at least one apparently positive result arising by chance. A prespecified strategy may address this, for example by defining a hierarchy or adjusting inference. The registry record does not report such a strategy or a statistical analysis plan.

The record identifies an intent-to-treat population for the primary endpoint but says the study was terminated before randomization. It does not report an analysis population for any outcome, the number with measurements, or how missing observations were handled. In general, missing-data methods depend on why measurements are absent and on assumptions about the missingness process. Those reasons and assumptions are not reported in the registry record, so no missing-data approach can be attributed to the trial.

The endpoint description also refers to the EAP, but that acronym is not expanded in the registry record. The record does not clarify its relationship to the stated intent-to-treat population or provide further analysis-population definitions. With zero analyses listed, there are no reported multiplicity-adjusted results, missing-data analyses or sensitivity analyses to interpret.

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

The record establishes what investigators planned to compare: CTAP101 extended-release capsules against placebo, using a responder endpoint based on a decrease in plasma iPTH. It also records a phase 3, multicenter, randomized and masked design. Those details describe the intended study question and structure, not evidence that the treatments were compared in randomized groups.

The record states that the study was terminated before randomization and lists zero analyses. It does not report whether participants met the primary response criterion, how group outcomes differed, or how uncertain any estimated difference would be. Thus, the posted information does not establish benefit, lack of benefit, equivalence or a safety difference. A missing treatment estimate must not be read as an estimate of no effect.

Likewise, the zero adverse-event counts in the listed groups do not show an absence of adverse events among exposed participants: both groups list zero participants at risk. Those entries do not support a comparative safety conclusion. The reason for termination is also not reported in the registry record, so it should not be taken as evidence of a particular concern or outcome.

In general, a trial’s planned endpoint can be statistically meaningful as a question even when the record does not contain data to answer it. Here, the threshold and timeframe are specified, but no randomized endpoint analysis is posted. The distinction is between a defined estimand—the treatment contrast the trial intended to assess—and an observed estimate based on analyzed participants. The record provides the former but not the latter.

12. Why This Trial Matters Statistically

This trial is statistically informative as an example of why intended design and completed analysis must be distinguished. The registry labels the study randomized and masked, but its primary endpoint description says termination occurred before randomization. A reader must therefore separate the planned comparison from the evidence actually reported. Design labels alone cannot establish that treatment effects were estimated.

The record also illustrates why enrollment should not be substituted for the randomized analysis population. Enrollment is listed as 2, but the record does not document treatment assignments, endpoint measurements or analyses. Without those elements, there is no reported group comparison and no basis for assessing its precision. The listed enrollment does not provide an efficacy denominator.

More generally, endpoint definitions, outcome listings and statistical conclusions are different parts of an evidence record. A clear responder threshold identifies the intended outcome, while a comparative estimate and its uncertainty are needed to describe the observed data. Here, the endpoint is defined and several secondary outcomes are named, but the registry lists zero analyses. The trial therefore demonstrates how a registry can document a scientific question without reporting a result that answers it.

The statistical lesson is not that a particular treatment effect is absent. Rather, the available record does not support an estimate of that effect. Recognizing this distinction prevents planned analyses, empty safety counts and a termination status from being mistaken for comparative findings.

13. 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 trial-specific limitation is that the registry states the study was terminated before randomization, while listing enrollment as 2. The record does not report who was enrolled, whether any participants received study treatment, or whether any primary endpoint measurements were available. It lists zero analyses, so no randomized comparison or estimate of precision can be assessed.

The record gives no reason for termination. It also does not report the trial-specific sample-size justification, detailed statistical analysis plan, randomization procedures, missing-data strategy or multiplicity approach. These omissions prevent assessment of whether the intended design was adequate for the primary question or how any incomplete observations might have been analyzed.

Some descriptions are incomplete or differ in wording. The masking field says triple, while the brief summary describes the study as double-blind; the record does not reconcile those terms. The cohort arm descriptions are empty, and EAP is not expanded. The study model is labeled sequential, but implementation details are absent.

The safety entries list zero participants at risk in both treatment groups, alongside zero affected participants and zero deaths. Those counts do not support a safety-rate estimate. Taken together, the record is useful for identifying the intended population, interventions and endpoint, but is insufficient for evaluating comparative efficacy or safety.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Phase 3 Safety and Efficacy Study of CTAP101 Extended-release Capsules in Children With Secondary Hyperparathyroidism — NCT05543928.
• Registry record last updated 2025-07-25; status last verified 2025-07.
• Results first posted 2025-07-25.
• 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.

17. Record Summary

The registry record describes a phase 3, multicenter study of CTAP101 extended-release capsules versus placebo in children ages 8 to <18 years with stage 3 or 4 chronic kidney disease, secondary hyperparathyroidism and vitamin D insufficiency. The intended primary endpoint was the proportion attaining a mean decrease in plasma iPTH of at least 30% from pretreatment baseline over 26 weeks.

The record lists randomized allocation, triple masking and a sequential model, and gives enrollment as 2. It also states that the study was terminated before randomization and lists zero analyses. No primary efficacy estimate, confidence interval, hypothesis-test result or comparative safety analysis is reported in the registry record. The reason for termination, detailed analysis methods and sample-size justification are not reported in the registry record.