A Single-dose Study in Paediatric Patients Aged 2 to Less Than 18 Years With Secondary Hyperparathyroidism (sHPT) Receiving Haemodialysis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Single-dose Study in Paediatric Patients Aged 2 to Less Than 18 Years With Secondary Hyperparathyroidism (sHPT) Receiving Haemodialysis (NCT02833857), a na phase 1 study. The primary outcome is Common Treatment-emergent Adverse Events.

2. Clinical Question

This is a safety and pharmacology study rather than a randomized comparison of treatments. The registry describes an open-label, single-dose investigation in children and adolescents with secondary hyperparathyroidism who were receiving maintenance haemodialysis. The primary outcome concerns common treatment-emergent adverse events. In the registry definition, such an event begins or worsens after the initial study dose and up to 30 days after the last dose; an event is called common if it occurs in at least 2 participants.

The record also lists secondary outcomes concerning changes in serum total and ionized calcium, etelcalcetide plasma concentrations and pharmacokinetic measures, and anti-etelcalcetide binding antibodies. These outcomes indicate the additional safety and pharmacology questions the study set out to assess. Their numerical results are not reported in the registry record.

Without a comparator, the study can describe observations following the dose but cannot isolate the effect of etelcalcetide from other influences or establish how outcomes would have differed under another treatment or no study drug. The posted safety counts are useful for understanding what was recorded in this small study, but they should be read as descriptive observations rather than a controlled estimate of treatment effect.

3. Trial Design

The registry identifies this as a Phase 1, open-label, single-group study. It lists no allocation to separate treatment arms and no masking. Participants received one intravenous bolus of etelcalcetide, 0.035 mg/kg, at the end of haemodialysis on study day 1. The registry lists an enrollment of 11 and marks the study completed. It records the study start as 2017-03-14 and primary completion as 2018-10-31.

The stated purpose was to evaluate safety and pharmacokinetics in paediatric patients with secondary hyperparathyroidism receiving a single dose at the end of haemodialysis. The official title also identifies tolerability and pharmacodynamics as study aims. The primary outcome is common treatment-emergent adverse events over a timeframe of 30 days. The safety analysis population is described as participants who received at least 1 dose of etelcalcetide.

Because this is a single-group study, the participants are not divided into randomized treatment and control groups. The safety record reports 11 participants in the etelcalcetide group as the denominator for its adverse-event summaries. There is no like-for-like control group against which to compare those counts. Consequently, the design is suited to describing events and pharmacology observed after dosing, but it does not provide a randomized estimate of comparative risk or benefit.

The registry record does not report a sample-size justification, details of an interim-analysis plan, or a fuller statistical analysis plan. The record also does not report methods for selecting the dose beyond the stated single-dose regimen. Those absences limit what can be said about the design rationale; they should not be filled by assuming customary procedures for studies of this type.

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: Participants who received at least 1 dose of etelcalcetide (safety analysis set)

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.

6. Primary Endpoint

The registry lists the primary outcome as Common Treatment-emergent Adverse Events, measured over 30 days.

The primary endpoint is titled “Common Treatment-emergent Adverse Events” and is measured as a count of participants. The registry defines a treatment-emergent adverse event as an adverse event that begins or worsens after the initial etelcalcetide dose and up to 30 days after the last dose. An adverse event is classified as common if it occurs in at least 2 participants. The record states that adverse events were coded using Medical Dictionary for Regulatory Activities version 21.0.

Counting participants with an event describes how many people experienced an event, rather than how many event episodes occurred. For a safety-focused study, this kind of endpoint can give a direct descriptive account of whether events were observed among those exposed to the study drug. The registry specifies the safety analysis set as participants who received at least 1 dose.

The posted summary distinguishes serious adverse events from other adverse events, but it does not give event-specific results for the primary endpoint’s common-event definition. The record therefore does not establish which particular events met that definition, nor does it provide their individual participant counts. Those event-level results are not reported in the registry record. The available aggregate counts should not be treated as a complete account of the primary endpoint’s event terms.

As a general statistical point, a count of participants with an event is descriptive. In a single-group study, it cannot by itself show whether an event was caused by treatment or whether its frequency is higher or lower than it would be under another condition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In a single-group study, participants receive the study intervention without a separate control group. The resulting summaries describe outcomes among those participants. They do not directly estimate a contrast between treatments. A randomized comparison is designed to make groups comparable, on average, with respect to factors that can affect outcomes. Since this study has no such comparator, a difference from an external expectation or from an unobserved alternative cannot be attributed to the study drug using the registry counts alone.

This distinction matters even when a safety outcome is counted objectively. A count can be accurately recorded while remaining difficult to interpret causally. The observed events may reflect the underlying condition, haemodialysis, other care, chance, or the study intervention. The record’s open-label designation also means masking was not used, but the registry does not describe how event assessment was conducted beyond its coding statement.

What does a participant count mean?

The primary outcome is expressed as the number of participants with an event, not the number of event episodes. If one participant experiences more than one event, a participant count and an episode count answer different questions. A participant count focuses on how many people were affected at least once; an episode count focuses on the total event burden. The registry lists the primary measure as a count of participants and defines the threshold for calling an event common. The event-specific counts needed to assess that definition are not reported in the registry record.

The denominator is important for interpreting any count. The registry defines the safety analysis set as participants who received at least 1 dose and reports 11 as the denominator for both serious and other adverse-event summaries. A count without its population and observation period can be misleading, so the registry’s stated 30-day timeframe and safety-set definition are part of the interpretation. The record does not provide additional details about participant-level follow-up or missing safety observations.

Why distinguish serious from other events?

Seriousness is a classification of an adverse event, distinct from whether it is common. A serious event may be uncommon, while a non-serious event may occur in several participants. The posted safety summary separates serious adverse events from other adverse events. The primary endpoint’s definition of common is based on occurrence in at least 2 participants; that threshold is not the same as the seriousness classification. The record does not report the event terms needed to see which specific non-serious events met the common-event threshold.

As a general statistical point, summaries of rare or infrequent events can be imprecise, especially in small studies. A zero count means that no event of that category was recorded in the observed participants during the reported assessment; it does not prove the underlying risk is zero. A count also does not reveal the range of plausible risks without an uncertainty analysis. No interval estimates are reported in the registry record.

What can pharmacology outcomes add?

The registry lists secondary outcomes for serum total calcium and ionized calcium changes, plasma concentration maximum and timing, area-under-the-curve measures, terminal half-life, and binding antibodies. In general, pharmacokinetic measures describe how drug concentration changes over time, while pharmacodynamic measures describe biological responses associated with exposure. The listed measures indicate the types of questions the study intended to address. Their numerical results, measurement schedules, and analysis methods are not reported in the registry record, so no conclusions about those outcomes can be drawn from the outcome list alone.

What do planning calculations mean?

In general, a sample-size calculation asks how many observations may be needed under specified assumptions to detect a chosen effect with a chosen statistical operating characteristic. The registry’s planning illustration specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those are assumptions for an illustration, not evidence that the actual study used a two-arm design. They also do not describe observed power. The record does not report the study’s own sample-size justification, and no trial-specific conclusion should be inferred from a hypothetical planning setup.

Over-dispersion is a general issue for count outcomes: it occurs when observed variability is greater than a simple model assumes. A model that understates variability can make uncertainty appear too small. The registry record does not report a count model or a dispersion estimate for this trial, and the posted primary measure is a participant count rather than a reported model-based treatment effect. It would therefore be inappropriate to claim that an over-dispersion adjustment was or was not applied.

Finally, significance tests and confidence intervals answer different but related questions. A test evaluates data against a specified null hypothesis; an interval describes uncertainty around an estimate. Neither resolves bias from the absence of a control group, missing outcome reporting, or limited information about event context. The registry record reports no analysis entries, so inferential methods for the listed outcomes are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and secondary outcomes covering calcium changes, pharmacokinetic measures, and binding antibodies. Considering several outcomes can create multiplicity: as a general statistical matter, the chance of at least one apparently unusual result may increase when many hypotheses are tested. Investigators may address this through a prespecified hierarchy, adjustment, or an explicitly exploratory interpretation. The registry record does not report a multiplicity strategy, so it is not possible to determine whether any adjustment was planned or used.

The record lists 22 outcome measures and 0 analysis entries. It does not report a statistical analysis plan describing how the outcomes were analyzed, how missing observations were handled, or whether any analyses were adjusted for participant characteristics. Those details are not reported in the registry record. The absence of an analysis entry should not be interpreted as evidence that an analysis was or was not performed outside the registry.

The stated safety analysis population consists of participants who received at least 1 dose of etelcalcetide. The adverse-event summaries use 11 as the denominator for serious and other events. The registry does not provide additional information about exclusions, withdrawals, incomplete follow-up, or missing safety data. It also does not report analysis populations for the secondary outcomes. As a result, the population underlying each listed pharmacology outcome cannot be established from the record.

For interpretation, the analysis population and missing-data approach matter because they determine who contributes to each result and what assumptions are made about unavailable observations. Without those methods and outcome-level results, the posted record supports only a limited descriptive reading of the adverse-event summaries.

11. 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 non-serious adverse event terms

The registry’s safety summary lists 0 participants with serious adverse events and 6 participants with other adverse events, with 11 as the denominator for each category. It does not list any serious adverse-event terms. The primary endpoint defines a treatment-emergent event by its timing after dosing and defines a common event as one occurring in at least 2 participants. The aggregate safety summary does not provide event-by-event counts, so it does not show which terms, if any, met the common-event threshold.

A serious adverse event and a common adverse event are not interchangeable categories. One describes seriousness; the other describes how often an event occurred among participants. The two summaries should therefore be read as distinct descriptions, not as competing measures of the same feature.

In general, a zero count is an observation in a particular study population and follow-up period, not proof that the event is impossible. These results also do not establish causation: the study has no control group, and the aggregate summary does not give clinical details for individual events. The registry record does not report event-specific narratives or a fuller account of follow-up. The counts should be understood within those limits, rather than as a complete characterization of safety.

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

The result supports a narrow descriptive statement: in the registry’s etelcalcetide safety summary, 0 participants were listed with serious adverse events and 6 were listed with other adverse events, using 11 as the denominator for each. The study evaluated a single intravenous dose of 0.035 mg/kg given at the end of haemodialysis. These observations describe the participants and assessment captured in the record.

They do not establish that etelcalcetide caused the reported events, nor do they show how event occurrence compares with another treatment or with no study drug. The study was open-label and single-group, with no randomized control arm. The counts therefore cannot support a comparative treatment-effect estimate. In general, an event occurring after treatment is not, by timing alone, proof that treatment caused it.

The result also does not establish the absence of risk. A zero serious-event count in this study means no serious adverse event was listed for the observed group in the posted summary; it does not show that serious events cannot occur in a larger or different population. The study’s size and the lack of event-level detail constrain what can be inferred about uncommon events, individual characteristics, or clinical context.

Nor do the posted safety figures answer the pharmacokinetic and pharmacodynamic questions named in the registry. Calcium changes, drug concentration measures, and antibody outcomes are listed, but their numerical results are not reported in the registry record. The record also provides no analysis entries or interval estimates for these outcomes. Their presence in the list of outcomes should not be mistaken for evidence that a particular change or relationship was observed.

Overall, the findings are best understood as limited descriptive safety observations from a single-dose study. They do not provide a controlled estimate of comparative safety, a causal conclusion, or a complete report of the stated pharmacology aims.

13. Why This Trial Matters Statistically

This study is statistically notable for the kind of evidence its design can produce. A Phase 1, open-label, single-group investigation can record safety events and characterize planned pharmacology outcomes after exposure. The design does not include a randomized comparator, so its primary contribution in the registry is descriptive rather than comparative. Keeping that distinction clear prevents a participant count from being interpreted as a treatment effect.

The endpoint definition also illustrates why outcome details matter. The registry calls events common when they occur in at least 2 participants, while the available safety summary groups events as serious or other. These are different classifications. Without event-specific counts, readers cannot map the aggregate safety figures directly onto the primary endpoint’s common-event definition. This is an important reporting limitation, not a reason to infer event terms that are absent from the record.

The trial’s listed secondary outcomes span safety, calcium response, drug exposure over time, and antibodies. Together, they reflect several distinct types of questions that require outcome-specific reporting and analysis. However, the registry record has no analysis entries, and numerical results for those secondary measures are not reported. The gap between outcomes listed and results reported shows why a registry record should be read both for what it states and for what it leaves unreported.

Finally, planning calculations based on a hypothetical two-arm setup should not be confused with the actual single-group design. A planning illustration does not amount to observed power or a justification for this study’s enrollment. The record does not report the study’s own sample-size rationale. Statistically careful interpretation depends on keeping design, outcome definitions, and available results aligned.

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 trial-specific limitation is the lack of a comparator. The registry records a single-group study with allocation listed as NA and masking as none. The observed adverse-event counts therefore cannot estimate a difference between etelcalcetide and another treatment, and they cannot separate treatment effects from other possible explanations for events.

The record gives aggregate serious and other adverse-event counts but does not report event-specific results for the primary endpoint’s common-event definition. It lists no serious-event terms. It also does not report event narratives or further timing and follow-up detail. This limits interpretation of the type, context, and course of the events.

Although secondary outcomes include calcium changes, etelcalcetide concentration measures, and binding antibodies, their numerical results are not reported in the registry record. No analysis entries are listed. Thus, the record does not permit assessment of those outcome results or their precision. The registry also does not report the statistical analysis plan, missing-data methods, multiplicity approach, interim analyses, or a sample-size justification.

The safety analysis set is defined as participants who received at least 1 dose, and the adverse-event summaries use 11 as the denominator. Further information about withdrawals, incomplete follow-up, or analysis populations for other outcomes is not reported in the registry record. These limitations mean the posted counts should be treated as a restricted descriptive summary, not a comprehensive account of all intended analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Single-dose Study in Paediatric Patients Aged 2 to Less Than 18 Years With Secondary Hyperparathyroidism (sHPT) Receiving Haemodialysis — NCT02833857.
• Registry record last updated 2019-07-10; status last verified 2019-04.
• Results first posted 2019-07-10.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed Phase 1, open-label, single-group study of etelcalcetide in paediatric patients aged 2 to less than 18 years with secondary hyperparathyroidism receiving maintenance haemodialysis. Participants received a single intravenous bolus of 0.035 mg/kg at the end of haemodialysis on study day 1. The listed enrollment is 11.

The primary outcome is common treatment-emergent adverse events over a 30-day timeframe. The safety summary lists 0 participants with serious adverse events and 6 with other adverse events, using 11 as the denominator for each. The registry also lists calcium, pharmacokinetic, and antibody outcomes, but their numerical results are not reported in the registry record.

The single-group design supports descriptive interpretation only. It does not provide a randomized comparison or a controlled estimate of comparative safety. The record does not report analysis entries, event-specific common-event results, or a fuller statistical analysis plan.