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 Open-label Study to Assess the Long-term Safety and Efficacy of Etelcalcetide (Also Known as AMG 416 or KAI-4169) in Patients With Secondary Hyperparathyroidism (NCT01576146), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01576146 |
| Phase | Phase 2 |
| Condition | Secondary Hyperparathyroidism |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | KAI Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
People with secondary hyperparathyroidism receiving hemodialysis who had completed 12 weeks of etelcalcetide treatment in the parent study.
Intervention
Etelcalcetide given by intravenous bolus injection three times a week at the end of each hemodialysis session, for up to 144 weeks in the extension.
Comparator
There was no comparator group. This was a single-group, open-label extension, not a randomized comparison.
Primary question
How many participants who received at least one extension-study dose had adverse events during the specified safety follow-up period?
The study record frames the purpose as evaluating long-term safety and efficacy. Its primary outcome is the number of participants with adverse events. The record separately lists changes from baseline in parathyroid hormone, serum corrected calcium, and serum phosphorus as secondary outcomes, but does not report numerical results for those outcomes.
Because every participant in the extension received etelcalcetide and there was no control group, the study can describe events observed during treatment but cannot make a like-for-like comparison with an untreated or differently treated group. Its open-label design also means participants and study staff were not masked to treatment. The registry record does not report a comparative primary question or a treatment-effect estimate against a control.
3. Trial Design
This was a phase 2, multicenter, open-label extension study with a single group. The registry lists enrollment of 30 and identifies etelcalcetide as the intervention. Participants were people with secondary hyperparathyroidism receiving hemodialysis who had completed 12 weeks of etelcalcetide treatment in the parent study. The extension was intended to evaluate longer-term safety and efficacy.
Etelcalcetide was administered as an intravenous bolus three times a week at the end of each hemodialysis session, for up to 144 weeks in the extension. The starting dose was the same as the final dose administered in the parent study. The dose was adjusted according to protocol-specific instructions, but the available description does not give those instructions in full.
There was no random allocation and no masking. The registry identifies the study as single-group, and no control arm is listed. Consequently, the results are descriptive of participants treated in this extension; they do not provide a randomized estimate of a difference between treatments. The record states that the study was terminated. It lists the study start as 2012-03 and primary completion as 2014-05-01.
The primary safety observation period began with the first dose in the parent study and continued through 30 days after the last extension dose. The reported actual median duration of treatment was 439 days. The safety population for the primary outcome is described as participants who received at least one dose of etelcalcetide in the extension. The registry record does not report the reason for termination, a detailed analysis plan, or further information about how participants entered or left the extension.
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: This study consisted of 40 weeks of treatment in extension period 1 followed by 2 years of additional treatment in extension period 2. The Sponsor ended the study early. Participants had the opportunity to rollover into another open-label extension study 20130213 (NCT02102204).
Extension Period 1
| Stage | Etelcalcetide |
|---|---|
| STARTED | 30 |
| COMPLETED | 20 |
| NOT COMPLETED | 10 |
Reasons for not completing this period:
| Reason | Etelcalcetide |
|---|---|
| Adverse Event | 2 |
| Death | 2 |
| Physician Decision | 2 |
| Withdrawal by Subject | 1 |
| Lost to Follow-up | 1 |
| Parathyroidectomy | 1 |
| Renal Transplant | 1 |
Extension Period 2
| Stage | Etelcalcetide |
|---|---|
| STARTED | 17 |
| COMPLETED | 0 |
| NOT COMPLETED | 17 |
Reasons for not completing this period:
| Reason | Etelcalcetide |
|---|---|
| Sponsor Decision | 13 |
| Death | 1 |
| Adverse Event | 1 |
| Renal Transplant | 1 |
| Treatment Not Resumed Within 8 Weeks | 1 |
Analysis population for the primary outcome, as defined in the registry: Participants who received at least one dose of etelcalcetide in the extension study
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: Baseline was defined as the baseline of the parent study, 20120331.
| Characteristic | Unit | Etelcalcetide |
|---|---|---|
| Participants analysed | 30 | |
| Age, Continuous | years | 55.4 (SD 14.2) |
| Sex: Female, Male: Female | Participants | 12 |
| Sex: Female, Male: Male | Participants | 18 |
| Race: Black (or African American) | Participants | 18 |
| Race: White | Participants | 12 |
| Ethnicity: Hispanic/Latino | Participants | 6 |
| Ethnicity: Not Hispanic/Latino | Participants | 24 |
| Parathyroid Hormone | pg/mL | 862.1 (SD 672.0) |
| Serum Corrected Calcium | mg/dL | 10.21 (SD 0.53) |
| Serum Phosphorus | mg/dL | 5.77 (SD 1.50) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events, measured over From the first dose of study drug in the parent study (20120331) through 30 days after the last dose in the extension study; actual median duration of treatment was 439 days..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is the number of participants with adverse events. It is a count of participants experiencing an event, rather than a measure of event severity, duration, or change in a laboratory value. The record defines the relevant population as those who received at least one dose of etelcalcetide in the extension. The observation window runs from the first dose in the parent study through 30 days after the last extension dose; the reported actual median treatment duration was 439 days.
Safety outcomes of this kind are used to describe the harms observed during exposure and follow-up. They can identify the frequency of participants recorded as having events and, when event terms are listed, indicate the types of serious events reported. They do not by themselves establish that treatment caused an event. In an uncontrolled study, underlying illness, dialysis, other treatments, and other circumstances cannot be separated from treatment effects using a comparison group.
The posted data distinguish participants with serious adverse events from those with other adverse events. They report 18 participants with serious adverse events and 27 with other adverse events among the 30 in the etelcalcetide group. These are separate categories in the record; they should not be added to form a total because the record does not establish whether the same participant appears in both categories. The listed secondary outcomes concern percent change from baseline in parathyroid hormone, serum corrected calcium, and serum phosphorus. Numerical estimates for those outcomes are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results report 18 participants with serious adverse events and 27 participants with other adverse events in the etelcalcetide group, which included 30 participants. These counts describe events recorded during the defined safety window; they do not estimate how many events etelcalcetide caused. The record gives no control group against which to judge whether the observed counts differ from what might occur without etelcalcetide or with another treatment.
The listed serious event terms include pneumonia at 13.3%, fluid overload at 10.0%, and angina pectoris, gastrointestinal haemorrhage, bacteraemia, and device related infection at 6.7% each. These percentages describe terms in the registry listing. They should not be read as mutually exclusive categories: a participant may have more than one serious event term. The registry record does not state whether the event-term percentages use all enrolled participants, participants with serious events, or another denominator, so no denominator should be inferred from the percentages alone.
The primary outcome counts do not convey the number of events per participant, the timing of each event, its duration, or its relationship to treatment. The record also does not report a death count. These details are important to a fuller interpretation of safety, and their absence means the available figures provide a limited description rather than a complete account of event experience.
The study is an open-label extension involving people who had already completed treatment in a parent study. This design can provide experience during longer exposure among those who entered the extension, but it does not represent a randomized test of treatment effects. The observed results may also reflect the characteristics of participants who continued into the extension; the registry record does not report details that would allow that selection to be assessed.
Although the registry lists secondary laboratory outcomes for parathyroid hormone, serum corrected calcium, and serum phosphorus, it does not report numerical results for them. No direction or magnitude of change, precision estimate, or statistical test for those outcomes can therefore be described. In particular, the study title and stated purpose do not substitute for posted numerical efficacy results. The evidence available in this record supports a description of the reported safety counts and study design, not a comparative conclusion about efficacy or causation.
9. Statistical Methods Explained
What does a count of participants with events represent?
The primary outcome is a participant count: it records whether participants were reported as having adverse events during the specified observation period. A participant count differs from an event count. One participant can experience multiple events, but the reported number of participants does not indicate how many events occurred in total or how often events recurred. It also does not describe how long an event lasted.
The record gives separate counts for serious and other adverse events. Those categories should be read as distinct reported summaries, not combined. If a participant experienced events in both categories, that participant could be represented in each summary. The record does not state whether the groups overlap, so adding the counts would not produce a justified total number of participants with any event.
What does an uncontrolled extension allow?
A single-group study describes outcomes among people receiving the intervention, but it lacks a concurrent group receiving a different treatment or no intervention. As a result, it cannot isolate the intervention's contribution to outcomes by comparing otherwise similar groups. Events observed during the study may have several possible explanations, including participants' health conditions, other care, or treatment exposure. The registry record does not provide a controlled contrast that could help distinguish these explanations.
The open-label design means treatment was not masked. Knowledge of treatment can influence reporting, assessment, and decisions about care. This is a general consideration in open-label studies, not evidence that any particular event was misclassified in this study. The registry record does not report procedures for event adjudication or masking of outcome assessors.
How should percentages for event terms be read?
The registry lists percentages next to selected serious event terms. A percentage is a proportion calculated using some denominator, but the denominator for these term-specific figures is not reported in the registry record. The listed percentages therefore should be quoted as reported, without converting them into participant counts or inferring which population they represent. Event terms can also overlap because one participant may experience more than one type of event. Adding percentages would not necessarily describe the share of participants with any serious event.
More generally, a confidence interval expresses the range of values reasonably compatible with an estimate under the statistical model used. It communicates precision as well as a point estimate. No confidence intervals for the reported event counts or term percentages are reported in the registry record. Without such intervals, the posted summaries do not quantify statistical uncertainty around those figures.
What is missing from the statistical description?
The registry record does not report a statistical analysis plan, hypothesis tests, p-values, confidence intervals, adjustment methods, or details about handling missing data. It also does not report interim analyses or a sample-size justification. The presence of enrollment information does not establish how that number was chosen or whether the study was designed to test a specified statistical hypothesis.
General statistical practice distinguishes a study's observed results from sample-size planning calculations. A planning illustration asks how many participants might be needed under stated assumptions; it is not a measure of observed power and does not establish what the study was designed to detect. The registry describes planning illustrations as based on an observed effect and as not representing the trial's own design. No planning figures or underlying effect estimates are reported in the registry record, so no numerical planning interpretation can be made from the available information.
The study lists percent change from baseline in parathyroid hormone, serum corrected calcium, and serum phosphorus as secondary outcomes, but no numerical findings or analysis details for these measures are reported in the registry record. Without estimates and measures of precision, their magnitude and uncertainty cannot be assessed. General considerations such as multiplicity may matter when several outcomes are examined: testing multiple outcomes can increase the chance of at least one apparently unusual finding. Whether any correction or other strategy was used in this study is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three secondary outcomes: percent change from baseline in parathyroid hormone, serum corrected calcium, and serum phosphorus. It does not report numerical results for these outcomes, including estimates, confidence intervals, or p-values. The record also identifies four outcome measures overall, but does not provide the analysis details needed to understand how each was evaluated.
When researchers examine multiple outcomes, there can be more opportunities for chance findings. A statistical plan may specify a primary outcome, testing order, or adjustment approach to address that issue. The registry record does not report whether multiplicity was considered or whether any adjustment was used. This absence does not show that an adjustment was or was not performed; the method is simply not reported in the registry record.
Missing-data methods and analysis populations beyond the stated primary safety population are also not described. The record defines that population as participants who received at least one dose of etelcalcetide in the extension, but does not explain how incomplete observations, withdrawal, or missing laboratory measurements were handled. It does not report reasons for termination or the extent of missing outcome data. As a result, the completeness and potential influence of missing observations cannot be assessed from 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 |
|---|---|---|---|
| Etelcalcetide | 18 | 30 | 60.0% |
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 |
|---|---|
| Etelcalcetide | 27 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | Etelcalcetide |
|---|---|---|
| Pneumonia | Infections and infestations | 4 of 30 |
| Fluid overload | Metabolism and nutrition disorders | 3 of 30 |
| Angina pectoris | Cardiac disorders | 2 of 30 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 2 of 30 |
| Bacteraemia | Infections and infestations | 2 of 30 |
| Device related infection | Infections and infestations | 2 of 30 |
| Osteomyelitis | Infections and infestations | 2 of 30 |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | 2 of 30 |
| Anaemia | Blood and lymphatic system disorders | 1 of 30 |
| Coagulopathy | Blood and lymphatic system disorders | 1 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Etelcalcetide |
|---|---|---|
| Blood calcium decreased | Investigations | 10 of 30 |
| Upper respiratory tract infection | Infections and infestations | 9 of 30 |
| Diarrhoea | Gastrointestinal disorders | 7 of 30 |
| Nausea | Gastrointestinal disorders | 5 of 30 |
| Seasonal allergy | Immune system disorders | 4 of 30 |
| Arteriovenous fistula site complication | Injury, poisoning and procedural complications | 4 of 30 |
| Hypocalcaemia | Metabolism and nutrition disorders | 4 of 30 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 4 of 30 |
| Pyrexia | General disorders | 3 of 30 |
| Cholelithiasis | Hepatobiliary disorders | 3 of 30 |
Serious events with the highest arm-level rate: pneumonia (13.3%), fluid overload (10.0%), angina pectoris (6.7%), gastrointestinal haemorrhage (6.7%), bacteraemia (6.7%).
The registry reports 18 participants with serious adverse events and 27 with other adverse events in the etelcalcetide group, which included 30 participants. These are participant counts, not totals of event episodes. The record does not say whether a participant could be counted in both categories, so the counts should not be added to create a combined total.
The selected serious event terms are reported as pneumonia at 13.3%, fluid overload at 10.0%, and angina pectoris, gastrointestinal haemorrhage, bacteraemia, and device related infection at 6.7% each. These term-specific percentages are not necessarily exclusive: one participant may have experienced more than one type of event. Their denominator is not reported in the registry record, so the percentages should not be converted into counts or interpreted as a share of a particular population.
The reported timeframe spans from the first dose in the parent study through 30 days after the last extension dose; actual median treatment duration was 439 days. The record does not report a death count or the relationship of individual events to treatment. These safety summaries describe what was recorded in an open-label, single-group extension; they do not establish that etelcalcetide caused the events or permit comparison with another treatment.
12. What the Result Does, and Does Not, Mean
The record documents a phase 2, open-label extension in which participants received etelcalcetide and reports counts of participants with serious and other adverse events. It also identifies selected serious event terms and lists laboratory measures intended as secondary outcomes. These details are useful for understanding the study's scope and the safety information entered in the registry.
The reported counts do not establish causation. Every participant in the extension received etelcalcetide, and there was no control group for a like-for-like comparison. The open-label design also does not provide masking. Therefore, these results cannot show whether the observed event counts were higher or lower than they would have been under another treatment or without etelcalcetide. They are descriptive results from the treated group, not a comparative treatment effect.
The registry record does not report numerical findings for the secondary changes in parathyroid hormone, serum corrected calcium, or serum phosphorus. It also does not provide confidence intervals or statistical tests for the safety summaries. Consequently, the available record does not establish the precision of the event counts or the magnitude of any laboratory changes. The study's stated aim to assess efficacy should not be mistaken for numerical evidence of efficacy when outcome results are not reported.
The findings also apply to an extension population: people receiving hemodialysis who had completed treatment in the parent study and then received at least one extension dose for inclusion in the primary safety population. The results do not necessarily describe people who did not enter or continue into the extension. The registry record does not report enough information to assess how such selection may affect interpretation.
In short, the posted data support a limited account of adverse events reported during the study and of its design. They do not establish treatment effects, event causation, comparative safety, or numerical efficacy results.
13. Why This Trial Matters Statistically
Longer-term extensions can add descriptive information about events observed during continued treatment after an earlier study. This record makes the extension's treatment context explicit: participants had completed 12 weeks of etelcalcetide in the parent study, and extension treatment was given at the end of each hemodialysis session for up to 144 weeks. The reported actual median duration of treatment was 439 days. Such exposure context helps readers understand the period over which the safety data were collected.
Statistically, the most important feature is that this was a single-group, open-label study. Its counts describe experience among treated participants, but there is no randomized comparator for estimating a between-group difference. This distinction matters because a number of events observed during treatment is not itself an estimate of treatment-attributable risk.
The record also illustrates why outcome reporting needs more than a study purpose or a list of planned measures. Although it lists secondary laboratory outcomes, numerical results and precision measures are not reported in the registry record. Without those estimates, readers cannot assess the magnitude or uncertainty of laboratory changes. Similarly, the absence of a reported analysis plan limits assessment of how outcomes and missing data were handled.
Finally, the serious event terms and their reported percentages offer a descriptive view of the types of events entered, but their denominator is not reported and event categories may overlap. Reading these figures carefully prevents them from being mistaken for a complete or comparative safety analysis. The study is therefore statistically informative chiefly as a description of an extension design and its posted adverse-event summaries, with important limits on inference.
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.
This study has no comparator group, no random allocation, and no masking. Its event counts cannot establish whether etelcalcetide caused an event or quantify a difference from another treatment. The open-label, single-group design also limits interpretation of subjective or assessment-dependent outcomes.
The extension enrolled people who had completed 12 weeks of treatment in the parent study. The results therefore concern participants who reached and entered the extension, rather than necessarily representing everyone who might receive treatment. The registry record does not report how participants who did not enter or continue were characterized, or provide details that would allow selection effects to be assessed.
The primary safety observation window includes time beginning with the first parent-study dose and extending through 30 days after the last extension dose, while the reported actual median treatment duration was 439 days. This context does not replace individual follow-up information. The record does not provide detailed event timing, duration, recurrence, relatedness to treatment, or a death count.
The serious event term percentages have no reported denominator, and the record does not clarify whether the same participant may contribute to multiple terms. It also does not report numerical results for the listed secondary laboratory outcomes. Statistical analysis methods, confidence intervals, missing-data handling, and the reason for termination are not reported in the registry record. These omissions constrain assessment of precision, completeness, and the interpretation of results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Open-label Study to Assess the Long-term Safety and Efficacy of Etelcalcetide (Also Known as AMG 416 or KAI-4169) in Patients With Secondary Hyperparathyroidism — NCT01576146.
- Registry record last updated 2017-04-13; status last verified 2017-03.
- Results first posted 2017-04-13.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry describes a phase 2, multicenter, open-label, single-group extension study of etelcalcetide in people with secondary hyperparathyroidism receiving hemodialysis who had completed treatment in a parent study. Enrollment was 30. Etelcalcetide was given by intravenous bolus injection three times a week at the end of hemodialysis, for up to 144 weeks.
The primary outcome was the number of participants with adverse events. The record reports 18 participants with serious adverse events and 27 with other adverse events. It lists serious event terms with percentages, but does not report their denominator. Secondary laboratory outcomes are listed without numerical results. The study status is terminated; the registry record does not report the reason.