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 Pharmacokinetics and Excretion of [¹⁴C]Etelcalcetide (AMG 416) in Patients With End Stage Renal Disease (ESRD) Receiving Dialysis (NCT02054572), a na phase 1 study. The primary outcome is Cumulative Excretion of Radioactivity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02054572 |
| Phase | Phase 1 |
| Condition | Secondary Hyperparathyroidism in Patients With ESRD on Hemodialysis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
Population
Patients with end stage renal disease receiving dialysis, in the context of secondary hyperparathyroidism. Six participants were enrolled. The primary endpoint population was participants who received any amount of radiolabelled etelcalcetide and had available excretion data.
Intervention
A single 10 mg dose of [¹⁴C]etelcalcetide, administered by intravenous bolus injection at the end of hemodialysis on day 1.
Comparator
There was no separate comparator group. The study was open-label and single-group, with no masking and no randomized allocation.
Primary question
How much administered radioactivity was recovered over time in excreta, dialysate, and the dialysis membrane, and how was it distributed across those routes? The study also aimed to measure radioactivity concentrations in whole blood and plasma over time.
This is a pharmacokinetic and excretion question rather than a treatment-versus-control question. The primary endpoint was cumulative recovery of radioactivity, expressed as a percentage of the administered dose, from day 1 to day 176. The endpoint description includes urine and feces as excreta and also includes dialysate and the dialysis membrane in the total radioactivity assessment. The study’s stated objectives encompass the rate, extent, and routes of radioactivity excretion.
The registry also lists secondary measures of etelcalcetide concentration and dialysis clearance. These include maximum observed concentration, its time of occurrence, last observed concentration, areas under the concentration curve, and hemodialysis clearance and extraction ratio. These measures address concentration over time and removal during dialysis, which are distinct from cumulative recovery of radioactivity. Numerical results for these measures are not reported in the registry record.
The clinical question is therefore descriptive: what happened to the measured radioactivity and drug concentrations after dosing in this small group? Without a comparator or reported endpoint values, the record cannot establish a comparative treatment effect or quantify the observed excretion profile.
3. Trial Design
This was a completed Phase 1, open-label, single-group study of radiolabelled etelcalcetide in patients with end stage renal disease receiving dialysis. The registry reports six participants enrolled. The intervention description specifies one 10 mg dose of [¹⁴C]etelcalcetide, given as an intravenous bolus at the end of hemodialysis on day 1. No masking was used, and allocation was listed as not applicable. The study began on 2014-02-07, and primary completion was recorded as 2014-04-15.
The design focused on measuring drug-related radioactivity and etelcalcetide concentrations over time, not on comparing two treatment groups. The primary endpoint covered day 1 to day 176 and assessed cumulative excretion. The registry describes radioactivity measurement in dialysate, the dialyzer, feces, and urine using accelerator mass spectrometry. It also states that radioactivity during days without sampling was estimated through interpolation and extrapolation of measured data.
Secondary outcomes covered concentration-time measures, including Tmax, Cmax, the last observed plasma concentration, and areas under the curve through 3 days and 10 days after dosing. Other listed outcomes concerned hemodialysis clearance and extraction ratio during hemodialysis on day 4. These are planned types of measurement in the registry record; numerical outcome results are not reported there.
Because all participants were in one group and received the same single-dose intervention, the design can describe measured pharmacokinetic and excretion patterns within the study population if results are available. It does not provide a concurrent untreated or active comparator for estimating a between-group effect. The registry record does not report a detailed statistical analysis plan, a sample-size justification, or interim analyses. No assumptions about those design choices can be made from the listed study description.
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
| Stage | [¹⁴C]Etelcalcetide |
|---|---|
| STARTED | 6 |
| COMPLETED | 6 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Participants who received any amount of \[¹⁴C\]etelcalcetide with available excretion data
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | [¹⁴C]Etelcalcetide |
|---|---|---|
| Participants analysed | 6 | |
| Age, Continuous | years | 56.3 (SD 16.4) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 3 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | participants | 0 |
| Race/Ethnicity, Customized: Asian | participants | 0 |
| Race/Ethnicity, Customized: Black (or African American) | participants | 5 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | participants | 0 |
| Race/Ethnicity, Customized: White | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Cumulative Excretion of Radioactivity, measured over Day 1 to day 176.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Percentage of administered dose |
| Endpoint classification | Continuous Endpoint |
The primary endpoint, cumulative excretion of radioactivity, measures total radioactivity recovered over time and expresses it as a percentage of the administered radioactive dose. The registry defines the assessment as the total radioactivity in excreta, meaning urine and feces, or in dialysate and the dialysis membrane. It reports that total radioactive counts in dialysate, the dialyzer, feces, and urine were determined by accelerator mass spectrometry (AMS). The time frame was day 1 to day 176.
This endpoint is used to describe the extent and routes of recovery of radiolabelled material after dosing. Radioactivity tracking can provide a measure of where the administered label is found, while concentration measurements address levels in blood or plasma. These are related but not interchangeable questions: cumulative recovery is not itself a plasma concentration or a measure of clinical benefit.
The registry specifies the endpoint as a mean with standard deviation. It also says that measurements for non-sampled days were estimated by interpolation and extrapolation from measured data. Consequently, the cumulative profile includes estimates for days without direct sampling, according to the described method. The endpoint’s participant population was those who received any amount of [¹⁴C]etelcalcetide and had available excretion data.
The registry record does not report the endpoint’s numerical mean, standard deviation, or route-specific recovery results. Thus, the measurement definition and collection approach are described, but the amount recovered and its precision cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a small, single-group pharmacokinetic and excretion study, with six participants enrolled and one stated dose of radiolabelled etelcalcetide. Its primary question concerns recovery of administered radioactivity over time, while secondary outcomes concern plasma concentrations and hemodialysis-related measures. These objectives are descriptive and do not involve a randomized comparison.
The most important interpretive point is that the primary endpoint’s numerical results are not reported in the registry record. The record identifies the endpoint, units, timeframe, population, and measurement approach, but does not provide a mean, standard deviation, or numerical recovery by route. Therefore, it is not possible to describe the observed amount or timing of excretion, compare routes, or judge the precision of an estimate from the registered information.
The same limitation applies to the listed secondary outcomes. The registry names concentration-time measures and dialysis clearance measures, but numerical values for them are not reported in the registry record. Listing an outcome does not establish its observed value or whether it was fully assessed in all participants. The record also does not report a detailed account of missing measurements or how any unavailable participant data were handled beyond defining the primary endpoint population as participants with available excretion data.
In general, a mean summarizes the central value of a continuous measurement, while a standard deviation describes variability among measured values. Neither can be interpreted without the actual estimate and the observations contributing to it. A confidence interval, when reported, would describe uncertainty around an estimate under its statistical assumptions; no primary endpoint confidence interval is reported in the registry record. The available description alone therefore cannot show how precisely cumulative recovery was estimated.
In general, a single-group study can characterize measurements collected after an intervention, but it does not separate the intervention’s effects from other influences using a control group. Here, the design is appropriate to the stated descriptive objectives, but it cannot provide a treatment contrast. The record also does not support claims about efficacy or comparative safety. The study’s stated objectives and listed measurements should be distinguished from results: without reported endpoint values, no conclusion about the observed excretion profile or concentration pattern can be drawn from the registry record.
Interpolation and extrapolation are part of the stated approach for non-sampled days. These methods estimate values between or beyond observed measurements based on the measured data and a chosen procedure. The registry description does not provide enough detail to assess the specific assumptions or their effect on the cumulative estimate. This matters especially for an endpoint accumulated over a long timeframe, because estimates for unmeasured days contribute to the reported total.
Overall, the record supports a description of the study’s question, design, endpoint definition, and safety-event counts. It does not report the numerical primary or secondary outcome results needed to characterize the measured pharmacokinetics or excretion. Interpretation should remain at that level rather than infer an outcome from the study’s objectives or methods.
9. Statistical Methods Explained
The registry identifies the primary endpoint as a continuous measure reported as a mean with standard deviation. It is cumulative radioactivity expressed as a percentage of the administered dose, assessed from day 1 to day 176. The endpoint description specifies measurements in dialysate, the dialyzer, feces, and urine. The registry says accelerator mass spectrometry was used to determine total radioactive counts in those materials, and that non-sampled days were estimated through interpolation and extrapolation.
What does a mean describe?
In general, the mean is the arithmetic average of a set of measurements and provides a summary of their central value. For cumulative excretion, a mean would summarize the endpoint values among the participants included in the analysis. It would not show whether participants had similar or very different individual values, so it is usually considered alongside a measure of variability. The numerical mean is not reported in the registry record.
What does the standard deviation add?
In general, the standard deviation describes how spread out observations are around their mean. A smaller standard deviation indicates observations closer to the mean, while a larger one indicates more variability. It is not the same as the uncertainty in the mean: standard deviation describes participant-level spread, whereas a confidence interval describes uncertainty about an estimated quantity under specified assumptions. The primary endpoint’s standard deviation is not reported in the registry record, so the degree of participant-to-participant variation cannot be assessed.
How should the percentage-of-dose scale be understood?
The endpoint uses the administered radioactive dose as its reference and reports recovered radioactivity relative to that dose. This makes the measure a description of recovery, not a direct measure of the concentration of etelcalcetide in plasma. The registry lists radioactivity in excreta and dialysis-related materials as part of the recovery assessment. A percentage-of-dose result would need to be read with its endpoint definition and measurement window; a numerical result is not reported in the registry record.
Why measure both radioactivity and drug concentration?
In general, radiolabel tracking and drug concentration measurements answer different pharmacokinetic questions. Radioactivity measurements track the label in collected materials and can be used to describe recovery by route. Concentration measurements describe the amount of etelcalcetide measured in a biological sample over time. The listed secondary outcomes include Tmax, the time to maximum observed concentration; Cmax, the maximum observed concentration; the time to and value of the last observed plasma concentration; and areas under the concentration curve through 3 days and 10 days after dosing. The registry lists these measures but does not report their numerical results.
The area under a concentration-time curve is, in general, a summary of measured concentration over a specified time interval. The registry’s listed intervals are from time zero to 3 days and from time zero to 10 days after dosing. Those outcomes describe concentration exposure over their respective intervals; they do not replace the longer-term cumulative recovery endpoint. Numerical values and precision estimates for these secondary measures are not reported in the registry record.
What do the dialysis measures address?
The registry lists hemodialysis clearance and extraction ratio for etelcalcetide during hemodialysis on day 4. In general, clearance describes removal from a measured compartment over time, while an extraction ratio describes the fraction removed across a process or passage. The registry’s listed outcomes identify the questions assessed, but it does not report the numerical estimates or their variability. The study description also specifies that the administered dose was given at the end of hemodialysis on day 1; this timing is part of the intervention description and should not be conflated with the day 4 dialysis measures.
What is the role of interpolation and extrapolation?
In general, interpolation estimates values between observed time points, and extrapolation estimates values outside the observed points. The registry states that radioactivity excreted during non-sampled days was estimated using both approaches based on measured data. These estimates allow an assessment across the stated timeframe, but they depend on how measured values are extended across unmeasured periods. The registry record does not report the detailed calculation procedure, assumptions, or sensitivity analyses for those estimates. Their influence on the final cumulative result therefore cannot be evaluated from the registered description.
What does the design allow statistically?
In general, a single-group design can describe observed measurements in the participants studied but cannot directly estimate a difference between an intervention and a control group. This study had no randomized allocation and no separate comparator group. Its stated purpose was to measure pharmacokinetics, biotransformation, and excretion after a single dose, rather than to test a comparative clinical outcome. The registry record does not report a detailed statistical analysis plan, the rationale for the enrollment size, or interim analyses.
The registry defines the primary endpoint population as participants who received any amount of [¹⁴C]etelcalcetide and had available excretion data. In general, restricting an analysis to participants with available data means the analyzed set may differ from the enrollment count if some participants lack usable measurements. The record does not report how many participants contributed to the primary endpoint or the numerical results. Accordingly, the stated enrollment should not automatically be treated as the endpoint analysis count.
In general, a confidence interval can communicate the uncertainty around an estimate and the range of values reasonably compatible with the data under its assumptions. It is not a guarantee that the true value lies in the interval, nor does it measure the spread among individual participants. No confidence interval for the primary endpoint is reported in the registry record. Without an estimate, variability, and uncertainty measure, the statistical precision of the primary result cannot be assessed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and multiple secondary outcomes, including concentration-time measures and dialysis clearance and extraction ratio. The number of listed outcome measures is 20, but a full list of their numerical findings is not reported in the registry record. The record reports no analyses. It does not describe a multiplicity adjustment, a hierarchy for interpreting secondary outcomes, or a prespecified procedure for controlling the chance of false-positive findings across multiple tests. Those details are not reported in the registry record and should not be inferred from the outcome list.
Missingness is relevant because the primary endpoint population is defined as participants who received any amount of radiolabelled etelcalcetide and had available excretion data. The registry does not state the number of participants included in that population or describe participant-level missingness, reasons for missing measurements, or a formal missing-data method. It does state that radioactivity for non-sampled days was estimated by interpolation and extrapolation of measured data; that is an approach to unobserved days in the collection profile, not a complete account of missing participant data.
In general, missing observations can affect estimates if the participants or time points without data differ systematically from those observed. Interpolation and extrapolation also rely on assumptions about values between or beyond measurements. The registry does not report sensitivity analyses evaluating these issues. The record does not provide enough information to determine the extent or impact of missing data on the primary endpoint.
The registry record also does not report a detailed analysis population for the secondary outcomes or explain how multiplicity was handled. These absences limit assessment of the prespecification and robustness of statistical conclusions. Since numerical outcome results are not reported in the registry record, there are no estimates in the record to evaluate for multiplicity or missing-data sensitivity.
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 |
|---|---|---|---|
| [¹⁴C]Etelcalcetide | 1 | 6 | 16.7% |
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 |
|---|---|
| [¹⁴C]Etelcalcetide | 5 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | [¹⁴C]Etelcalcetide |
|---|---|---|
| Pneumonia | Infections and infestations | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | [¹⁴C]Etelcalcetide |
|---|---|---|
| Constipation | Gastrointestinal disorders | 2 of 6 |
| Flatulence | Gastrointestinal disorders | 1 of 6 |
| Nausea | Gastrointestinal disorders | 1 of 6 |
| Vomiting | Gastrointestinal disorders | 1 of 6 |
| Upper respiratory tract infection | Infections and infestations | 1 of 6 |
| Dermatitis contact | Skin and subcutaneous tissue disorders | 1 of 6 |
Serious events with the highest arm-level rate: pneumonia (16.7%).
The safety listing reports one serious adverse event among six participants at risk in the [¹⁴C]etelcalcetide group. It lists five participants with other adverse events among six at risk. These are separate registry categories; the record does not establish from these counts whether participants in one category also appear in the other. The most frequent serious adverse-event term listed is pneumonia, reported as 16.7%.
These figures describe event reporting in a group of six participants. They are not a comparison with another group, because the study had no comparator. The counts do not establish whether an event was caused by the study intervention. The registry record does not provide additional event-level detail in the registry record for this analysis, such as timing, severity beyond the serious classification, or a causal assessment.
The death count is not reported in the registry record. A missing death count should not be interpreted as confirmation that there were no deaths. More broadly, safety counts in a small, single-group study describe what was recorded for participants in that study; they cannot by themselves establish a comparative risk estimate. The listed serious-event percentage should be read as the registry’s reported value, without treating it as a result from a controlled comparison.
12. What the Result Does, and Does Not, Mean
This study’s registered purpose was to characterize the rate, extent, and routes of radioactivity excretion after a single dose of radiolabelled etelcalcetide in patients with end stage renal disease receiving dialysis. The primary endpoint was cumulative recovery of radioactivity over day 1 to day 176. Secondary outcomes addressed etelcalcetide concentration over time and hemodialysis clearance measures. These are pharmacokinetic and excretion questions, not direct tests of clinical benefit.
The registry record describes a single-group, open-label design with six participants enrolled and no comparator. That design can support description of measurements in the participants studied when numerical results are reported. It cannot provide a randomized estimate of how outcomes differ from a control group. The record does not report the primary endpoint’s numerical result, its standard deviation, or numerical findings for the secondary outcomes. As a result, the observed excretion pattern, concentration profile, and precision of estimates cannot be characterized from the registered information.
The methods description states that radioactivity was measured in dialysate, the dialyzer, feces, and urine using accelerator mass spectrometry, and that estimates for non-sampled days used interpolation and extrapolation. These details explain how the endpoint was intended to be assessed, but they do not supply the outcome values or establish how well the estimates represent the full time course.
The safety listing reports one serious adverse event among six participants at risk and five participants with other adverse events among six at risk, with pneumonia listed at 16.7% as a serious-event term. These observations describe event reporting in this study group. Without a comparator, they do not estimate a comparative safety difference. The death count is not reported in the registry record.
Accordingly, the record can establish the question, design, measurement definitions, and listed safety counts. It cannot establish a numerical excretion result, demonstrate a treatment effect, or support a conclusion about comparative clinical outcomes. The absence of reported results is an information limitation, not evidence that an outcome was absent or unchanged.
13. Why This Trial Matters Statistically
Pharmacokinetic studies in populations with end stage renal disease receiving dialysis raise measurement questions that differ from those in a comparative treatment trial. This study’s primary objective was to describe radioactivity recovery and its routes after a single radiolabelled dose. The registry also lists plasma concentration and hemodialysis measures. Separating these questions statistically is important: cumulative recovery, concentration over time, and removal during dialysis are not interchangeable endpoints.
The primary endpoint’s definition includes multiple collection materials and a long assessment window, from day 1 to day 176. The registry states that non-sampled days were estimated by interpolation and extrapolation. This makes the time structure of measurement part of the interpretation: an accumulated endpoint may combine directly measured values with estimates for days without sampling. General statistical reasoning therefore calls for clarity about the data contributing to the total and the assumptions used to fill time gaps. The registry describes the broad approach but does not report its detailed implementation or sensitivity analyses.
The single-group design is another key statistical feature. It is aligned with descriptive pharmacokinetic objectives, but it does not generate a randomized contrast against another group. The six enrolled participants also define a small study population, so any reported summary would need to be interpreted in its specific study context. The registry’s numerical outcome results are not reported, preventing assessment of estimates, participant variability, or precision.
Finally, the record’s distinction between stated objectives and reported results matters. An outcome can be named and a measurement method described without a numerical result being available. Careful reading avoids turning a study aim into a finding and avoids interpreting a missing result as a null result. For statistical interpretation, the record is informative about design and endpoint construction, but not about the observed magnitude of the primary excretion outcome.
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 interpreting this study is that numerical results for the primary endpoint are not reported in the registry record. Although the endpoint, unit, timeframe, and measurement methods are described, the mean and standard deviation are absent. Route-specific cumulative recovery values are also not reported, so the relative contribution of urine, feces, dialysate, and the dialysis membrane cannot be assessed. Numerical values for the listed secondary concentration and dialysis measures are not reported either.
The study was single-group and open-label, with no comparator and no randomized allocation. This is consistent with its descriptive pharmacokinetic and excretion objectives, but it means there is no concurrent control for a treatment contrast. The enrollment was six participants, and the primary analysis population was defined by receipt of any amount of radiolabelled etelcalcetide and availability of excretion data. The registry does not report the number contributing to that endpoint analysis, so the enrolled group and analyzed group cannot be assumed to be identical.
The primary endpoint covers day 1 to day 176 and includes estimates for non-sampled days through interpolation and extrapolation. The registry does not describe the detailed estimation procedure, the assumptions used, or sensitivity analyses addressing the effect of estimated values. It also does not report participant-level missingness, reasons for unavailable measurements, or a missing-data analysis plan.
The registry record does not report a detailed statistical analysis plan, sample-size justification, interim analyses, or a multiplicity procedure for the listed outcomes. The death count is not reported. These omissions limit assessment of analysis choices and safety completeness. They should be treated as unreported information, not as evidence that a particular method was or was not used, or that an event did or did not occur.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics and Excretion of [¹⁴C]Etelcalcetide (AMG 416) in Patients With End Stage Renal Disease (ESRD) Receiving Dialysis — NCT02054572.
- Registry record last updated 2018-08-31; status last verified 2018-08.
- Results first posted 2017-04-14.
- 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
NCT02054572 is a completed Phase 1, open-label, single-group study of radiolabelled etelcalcetide in patients with end stage renal disease receiving dialysis. Six participants were enrolled. Participants received a single 10 mg intravenous bolus at the end of hemodialysis on day 1. The study began on 2014-02-07, with primary completion on 2014-04-15.
The primary endpoint was cumulative radioactivity excretion, expressed as a percentage of the administered dose from day 1 to day 176. Radioactivity was assessed in dialysate, the dialyzer, feces, and urine, with non-sampled days estimated by interpolation and extrapolation. Secondary outcomes concerned etelcalcetide concentrations and hemodialysis measures.
Numerical primary and secondary outcome results are not reported in the registry record. The safety listing reports one serious adverse event among six participants at risk and five participants with other adverse events among six at risk; pneumonia is listed at 16.7% among serious-event terms. The death count is not reported in the registry record.