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 A Safety and Tolerability Study of Zerenex (Ferric Citrate) in Patients With End-Stage Renal Disease (ESRD) (NCT00648167), a na phase 2 study. The primary outcome is The Difference in Serum Phosphorus Between Baseline (Day 0) and End of Treatment (Day 28).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00648167 |
| Phase | Phase 2 |
| Condition | Hyperphosphatemia, End-stage Renal Disease |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 55 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Keryx Biopharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Patients with end-stage renal disease (ESRD) and hyperphosphatemia. The registry record lists 55 participants enrolled; further eligibility details, such as age criteria and baseline clinical characteristics, are not reported in the registry record.
Intervention
Ferric citrate, identified in the record as Zerenex and KRX-0502. Participants were to switch from their current phosphate binder and have the dose titrated to the maximum tolerated dose, up to about 12g/day, based on serum phosphorus levels.
Comparator
There was no concurrent control group. The endpoint compares serum phosphorus at baseline (Day 0) with the end of treatment (Day 28) in the single-group study. The record does not describe a randomized or like-for-like comparison with another treatment.
Primary question
What was the difference in mean serum phosphorus between baseline (Day 0) and the end of treatment (Day 28), and what safety and tolerability events were recorded during the study? The numerical endpoint result and its statistical analysis are not reported in the registry record.
This question is narrower than asking whether ferric citrate is better than another treatment. The design listed is single-group, with no masking and allocation recorded as NA. The registry therefore describes a treatment period and a before-and-after endpoint, rather than a randomized comparison against a concurrent control. Any change between baseline and Day 28 would need to be interpreted in light of that design, the participants’ switch from their current phosphate binder, and the dose titration based on serum phosphorus.
The study’s stated focus is safety and tolerability in ESRD with hyperphosphatemia. The registry lists one primary outcome measure, a continuous measure of serum phosphorus expressed in mg/dL, with a timeframe of 28 days. It does not report the observed mean difference, the standard deviation associated with the endpoint, or a confidence interval or p-value. It also does not report a detailed definition of the analysis population or the specific analysis method. These omissions limit what can be concluded about the observed endpoint from the registry record.
3. Trial Design
This is a completed Phase 2 study sponsored by Keryx Biopharmaceuticals. The registry lists 55 participants enrolled and identifies hyperphosphatemia and end-stage renal disease as the conditions. The recorded study start is 2008-03, and primary completion is listed as 2009-01. The study title and summary describe an assessment of the safety and tolerability of Zerenex (ferric citrate) for hyperphosphatemia in patients with ESRD.
The design is recorded as single-group, with allocation listed as NA and masking listed as none. The intervention is ferric citrate, also called KRX-0502 in the arm description. Participants were to switch from their current phosphate binder to Zerenex and be titrated to the maximum tolerated dose, up to about 12g/day, based on serum phosphorus levels. The record does not describe a separate control arm or a randomized assignment process. The number of study sites and details of treatment administration beyond this description are not reported in the registry record.
The listed primary outcome is the difference in serum phosphorus between baseline (Day 0) and the end of treatment (Day 28), measured in mg/dL and described as a mean with standard deviation. The timeframe is 28 days. The registry lists one outcome measure but no analyses. It does not provide the endpoint’s numerical estimate, participant-level data, or an explanation of how the mean difference was calculated.
Because this is a single-group study, the baseline measurement serves as the reference for the stated endpoint; it is not a concurrent control group. Changes over the treatment period cannot by themselves isolate the effect of ferric citrate from other influences that could affect measurements over time. The registry record does not report a protocol, a sample-size justification, interim analyses, or a detailed statistical analysis plan. The listed enrollment is the study’s enrolled sample, not a basis for claiming a particular degree of statistical power.
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 | KRX-0502 |
|---|---|
| STARTED | 55 |
| Start Dose 4.5 g/Day | 34 |
| Start Dose 6 g/Day | 21 |
| COMPLETED | 48 |
| NOT COMPLETED | 7 |
Reasons for not completing this period:
| Reason | KRX-0502 |
|---|---|
| Adverse Event | 6 |
| unable to swallow tablets | 1 |
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: Intent-to-Treat
| Characteristic | Unit | KRX-0502 |
|---|---|---|
| Participants analysed | 55 | |
| Age, Continuous | years | 53.46 (SD 11.48) |
| Sex: Female, Male: Female | Participants | 23 |
| Sex: Female, Male: Male | Participants | 32 |
| Region of Enrollment: United States | participants | 50 |
| Region of Enrollment: Puerto Rico | participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as The Difference in Serum Phosphorus Between Baseline (Day 0) and End of Treatment (Day 28), measured over 28 days.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mg/dL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the difference in mean serum phosphorus between baseline (Day 0) and the end of treatment (Day 28), with the concentration expressed in mg/dL. It is listed as a continuous measure summarized by a mean and standard deviation, over a timeframe of 28 days. The registry describes the outcome but does not state the observed difference or its direction and magnitude.
Serum phosphorus is the measured quantity named in the trial’s stated focus on hyperphosphatemia. Tracking it at baseline and the end of treatment gives a way to describe how the measured concentration changed over the study period. In general, a continuous endpoint retains information about measured values rather than reducing them to a simple event count. A mean describes the central value of a group of measurements, while a standard deviation describes how dispersed those measurements are around the mean.
The record does not specify whether the reported difference was calculated from each participant’s paired measurements, from group means at each visit, or by another method. In general, paired measurements can be analyzed by calculating an individual change for each participant and then summarizing those changes; that approach accounts for the relationship between measurements from the same person. Whether that was the method used in this study is not reported in the registry record.
The endpoint is a laboratory measure, not a direct description of every aspect of safety, tolerability, or health status. The endpoint alone would not establish how participants felt, whether other outcomes changed, or how the treatment compares with an alternative. No numerical estimate or uncertainty measure for the primary endpoint is reported in the registry record, so its observed size and precision cannot be described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a primary endpoint and a treatment timeframe, but does not report the numerical endpoint result or an analysis. Consequently, the record does not establish the average serum phosphorus difference between baseline and Day 28, the variability in that difference, or the precision of an estimate. It also does not report a confidence interval or a p-value. Without those results, the endpoint cannot be characterized as having increased, decreased, or remained similar on the basis of the posted registry information.
The distinction between an endpoint definition and an endpoint result matters. The outcome title indicates what was intended to be measured; it is not evidence of what the participants’ measurements showed. The registry lists one outcome measure and zero analyses. That means the record contains no reported statistical analysis for the primary outcome. It does not establish whether analyses were performed elsewhere or whether results were published outside this registry record.
The single-group design also determines what any before-and-after result could mean. In general, comparing a group with its own baseline can describe change over time, but it does not provide a concurrent estimate of what would have happened without the intervention. Here, participants were to switch from their current phosphate binder and have ferric citrate titrated based on serum phosphorus. The record does not describe how other influences on the measurements were assessed. A baseline comparison therefore should not be read as equivalent to a randomized comparison between treatments.
The registry lists 55 participants enrolled. That figure gives the recorded enrollment but does not show how many contributed endpoint measurements, how missing measurements were handled, or which participants were included in any analysis. Those details are not reported in the registry record. The enrollment number alone does not demonstrate that the study could detect a particular effect, and it is not an observed-power result.
Safety information is also limited to the posted counts and serious-event terms. The record lists 4 participants affected by serious adverse events among 55 at risk, and lists other adverse events in 46 participants among 55 at risk. It names several serious-event terms with a reported frequency of 1.8% each. These entries describe the registry’s safety reporting; without fuller definitions, follow-up details, or an analysis, they do not determine whether an event was caused by treatment. Deaths are not reported in the registry record.
Overall, the available record supports a description of the study design, intended endpoint, and selected safety counts. It does not support a quantitative conclusion about the primary endpoint or a treatment comparison. The absence of a posted estimate is a limitation of the record’s results, not evidence that the endpoint had no change.
9. Statistical Methods Explained
The registry describes a continuous primary outcome: the difference in mean serum phosphorus from baseline (Day 0) to the end of treatment (Day 28), measured in mg/dL. It states that the outcome is summarized as a mean and standard deviation. These terms describe the type of measurement and a possible summary, but the registry does not report the estimate or its standard deviation. The analysis method used to produce the endpoint is not reported in the registry record.
What does a mean describe?
In general, a mean is an average that summarizes the level of a continuous measurement across a group. It can be useful for describing the center of a distribution, but it does not show the full range of individual values or whether the measurements cluster closely together. A standard deviation describes dispersion around the mean. A relatively larger spread means individual measurements vary more around that group average; the standard deviation is not itself an estimate of uncertainty in the mean.
For a before-and-after endpoint, a mean difference can be defined in different ways. In general, an analysis may calculate a change for each participant and then summarize those changes, or compare group summaries at separate time points. If the same participants have measurements at both time points, their measurements are related. A paired analysis can use that relationship. The registry does not state which calculation was used, whether all participants had both measurements, or whether any adjustment was made.
How should uncertainty be understood?
In general, a confidence interval gives a range of values compatible with the observed data and the assumptions of the analysis. Its width conveys precision: a narrower interval indicates greater precision under those assumptions, while a wider interval indicates greater uncertainty. A p-value, when reported, measures how unusual the data would be under a specified null model; it is not the probability that a treatment works or that the null hypothesis is true. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record.
Statistical significance and clinical importance are also distinct concepts. In general, statistical significance concerns compatibility with a statistical null model, whereas clinical importance depends on whether the magnitude of a change matters in the relevant clinical context. The record does not state a threshold for a clinically important difference or report an endpoint estimate that could be compared with such a threshold. No conclusion on either point can be drawn from the endpoint definition alone.
What does the design allow?
The recorded model is single-group, with no masking and allocation listed as NA. There is no concurrent control arm described. In general, a within-group baseline comparison can show that measurements differ over time, but it cannot separate treatment effects from other changes that occur over that period. The intervention description adds that participants switched from their current phosphate binder and were titrated to the maximum tolerated dose based on serum phosphorus. The record does not report a protocol explaining the titration rules in further detail or the analysis method used to account for titration.
The sample-size assumptions described for planning illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe detecting a stated fraction of the observed effect. These are assumptions for planning illustrations, not a description of the single-group trial’s observed analysis. The record does not report the study’s own sample-size justification or indicate that these planning assumptions formed part of its design. Any sample-size figure calculated under such assumptions is a planning illustration, not observed power. Participants per arm for 80% power is a planning quantity, not the number enrolled in this study.
In general, a normal approximation is a mathematical simplification that can be used to estimate sampling behavior under stated conditions. It may be reasonable for some planning calculations, but the registry does not describe diagnostic checks or the distribution of the endpoint. Equal allocation between two arms is a planning assumption that does not match the listed single-group structure. These assumptions should therefore not be mistaken for evidence that the trial enrolled two arms or used a two-arm inferential test.
What analysis details are absent?
The registry lists no analyses. It does not report a statistical analysis plan, the exact analysis population, methods for handling missing observations, covariate adjustment, sensitivity analyses, or interim analyses. It also does not state whether the outcome was analyzed as a change score or by another model. These missing details affect how an estimate would be interpreted and reproduced. No statistical method should be attributed to the trial without a report of that method.
Multiplicity refers, in general, to the increased chance of obtaining a chance-positive result when many outcomes or statistical tests are considered. The record lists one primary outcome measure, but it does not describe the full set of planned analyses, any secondary outcomes, or multiplicity adjustments. It is therefore not possible to assess the complete testing strategy from the registry record. The number of listed primary outcomes alone does not establish that no other analyses were planned or performed.
Finally, a registry entry is not a substitute for participant-level data or a complete statistical report. The posted details identify the outcome and some design features, but not the analysis needed to quantify a treatment-period change. Any inference about the endpoint’s size, precision, or statistical significance would require results that are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure, the difference in mean serum phosphorus between baseline (Day 0) and the end of treatment (Day 28). It lists zero analyses. A detailed statistical analysis plan, the full set of planned outcomes and tests, and any adjustment for multiple testing are not reported in the registry record.
In general, multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. Repeated testing can make chance findings more likely unless the analysis plan accounts for the number and structure of tests. The registry entry does not provide enough information to determine whether multiplicity was an issue in the full study or how it may have been handled. The count of one listed primary outcome does not reveal the complete analysis strategy.
The handling of missing data is also not reported in the registry record. The record does not state how many participants had serum phosphorus measurements at baseline and Day 28, whether participants discontinued treatment, or how missing endpoint measurements were treated. It does not specify whether an analysis used all enrolled participants, only participants with available measurements, or another defined group.
The analysis population is not reported in the registry record. In general, this definition matters because it identifies who contributes to the estimate and how departures from the planned treatment period are handled. The listed enrollment of 55 should not be assumed to equal the number included in the endpoint analysis. Nor does the enrollment figure establish that data were complete or that a particular missing-data method was used.
Because no endpoint analysis is listed, the record does not allow assessment of how these choices influenced a result. The absence of reporting should not be interpreted as evidence that there were no missing observations or no additional analyses.
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 |
|---|---|---|---|
| KRX-0502 | 4 | 55 | 7.3% |
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 |
|---|---|
| KRX-0502 | 46 of 55 |
Most frequent serious adverse event terms
| Event term | Organ system | KRX-0502 |
|---|---|---|
| Liver infection | Infections and infestations | 1 of 55 |
| Methicillin - susceptible staphylococcus aureus bacteremia | Infections and infestations | 1 of 55 |
| Suicide attempt | Psychiatric disorders | 1 of 55 |
| Worsened congestive heart failure | Cardiac disorders | 1 of 55 |
Most frequent non-serious adverse event terms
| Event term | Organ system | KRX-0502 |
|---|---|---|
| Stool color abnormality | Gastrointestinal disorders | 34 of 55 |
| Diarrhea | Gastrointestinal disorders | 14 of 55 |
| Constipation | Gastrointestinal disorders | 11 of 55 |
| Nausea | Gastrointestinal disorders | 5 of 55 |
| Vomiting | Gastrointestinal disorders | 5 of 55 |
| Bloating | Gastrointestinal disorders | 4 of 55 |
| Heartburn | Gastrointestinal disorders | 4 of 55 |
| Stomach pain or cramp | Gastrointestinal disorders | 4 of 55 |
| Increased appetite | Gastrointestinal disorders | 3 of 55 |
Serious events with the highest arm-level rate: liver infection (1.8%), methicillin - susceptible staphylococcus aureus bacteremia (1.8%), suicide attempt (1.8%), worsened congestive heart failure (1.8%).
The registry lists 55 participants at risk for serious adverse events and 4 participants affected. It also lists 55 at risk for other adverse events and 46 affected. These are participant counts in the KRX-0502 group. They are distinct safety summaries; the record does not explain how event categories were defined or whether a participant could appear in more than one category.
The registry lists four serious-event terms, each with a frequency of 1.8%: Liver infection, Methicillin - susceptible staphylococcus aureus bacteremia, Suicide attempt, and Worsened congestive heart failure. The record does not provide further details about timing, severity beyond the serious-event classification, duration, outcome, or attribution to treatment. The listed terms and frequencies should be read as registry entries, not as evidence that ferric citrate caused those events.
Deaths are not reported in the registry record. That is different from a reported count of zero. The safety summary also does not provide a comparison group, so it cannot show whether event counts differed from those under another treatment or no treatment. In general, event counts describe what was recorded in the observed group; interpretation depends on the definitions, follow-up, completeness of reporting, and study design. Those details are not fully in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed Phase 2, single-group study enrolled 55 participants and assessed ferric citrate in patients with ESRD and hyperphosphatemia. It identifies a primary endpoint based on serum phosphorus at baseline and at the end of a 28-day treatment period. It also records selected safety counts and serious adverse-event terms. These registry entries describe the study’s stated purpose, design, outcome, and posted safety information.
The record does not report the numerical result for the primary endpoint. It therefore does not show the magnitude, direction, or precision of the mean serum phosphorus difference. No confidence interval, p-value, or analysis is listed. The missing result cannot be interpreted as evidence of no change, nor can it support a claim about the size or reliability of any change.
The single-group structure is important. A baseline-to-endpoint comparison can describe change within the enrolled group, but without a concurrent control it cannot establish how the outcome would have changed over the same period under another treatment or without the intervention. Participants were to switch from their existing phosphate binder and receive a titrated ferric citrate dose. The record does not report methods that would separate the effects of treatment from other influences on measurements over time.
The safety counts provide a limited description of events recorded in the group. They do not establish causation or comparative safety. The registry does not report deaths, which is not the same as documenting none. It also does not provide enough detail to determine the completeness of event collection or the circumstances of the listed serious events.
Thus, the posted information is useful for understanding what the study set out to assess and the broad structure of its design. It does not provide the outcome analysis needed to quantify the primary endpoint or support a treatment comparison. A complete interpretation would require endpoint results, analysis details, and fuller information about participants and safety follow-up, none of which are reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates why design and result reporting need to be read together. The endpoint is defined as a change in mean serum phosphorus from baseline to the end of treatment, but the record does not report the measured change or its uncertainty. An outcome definition tells readers what investigators planned to assess; it does not reveal what the data showed. That distinction is central when interpreting registry entries.
The single-group model also provides a useful statistical example. Repeated measurements in the same participants can describe change over time, but a before-and-after comparison is not the same as a comparison against a randomized control group. In this record, the intervention also involves switching from each participant’s current phosphate binder and titrating ferric citrate based on serum phosphorus. Understanding that treatment process is relevant to interpreting any observed change, but the posted endpoint analysis is absent.
The record further demonstrates the difference between enrollment and analysis. It lists 55 participants enrolled, while the number contributing data to the primary endpoint and the analysis population are not reported. Enrollment alone cannot establish endpoint completeness, precision, or power. Planning illustrations based on assumptions are also distinct from the study’s actual design and from an observed analysis.
Finally, the safety summary shows why counts need context. The posted serious and other adverse-event counts describe events recorded in a single group. Without a concurrent control and additional information about follow-up and event attribution, these counts cannot quantify comparative risk or establish causality. Careful statistical reading means describing what is recorded while avoiding conclusions that require unreported analyses or comparison data.
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 most important limitation for statistical interpretation is that the registry does not report the numerical primary endpoint result. Although the outcome is specified as the difference in mean serum phosphorus between baseline (Day 0) and Day 28, the estimate, standard deviation, confidence interval, and p-value are not reported in the registry record. The record also lists no analyses, so the calculation and inferential method cannot be assessed.
The single-group design does not include a concurrent control, and allocation is listed as NA. The record therefore does not describe a like-for-like comparison with another treatment. The intervention included a switch from participants’ current phosphate binder and titration according to serum phosphorus, but the detailed procedures and statistical treatment of those features are not reported.
The enrolled sample is listed as 55, but the number with endpoint data, the analysis population, participant characteristics, and handling of missing measurements are not reported in the registry record. The registry does not describe the sample-size justification, interim analyses, or detailed statistical plan. It is not possible to determine the study’s precision from the enrollment figure alone.
Safety reporting is also limited. The record lists affected-participant counts and several serious-event terms, but details about follow-up, event definitions, timing, outcomes, and treatment attribution are not reported. Deaths are not reported in the registry record. There is no control group for a comparative safety assessment, and the listed frequencies do not by themselves establish causality.
These limitations concern what can be inferred from the registry record. They do not establish that unreported analyses or data do not exist elsewhere; they mean those details cannot be evaluated from this record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Safety and Tolerability Study of Zerenex (Ferric Citrate) in Patients With End-Stage Renal Disease (ESRD) — NCT00648167.
- Registry record last updated 2017-04-04; status last verified 2017-03.
- Results first posted 2014-10-09.
- 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 record describes a completed Phase 2 study sponsored by Keryx Biopharmaceuticals, with 55 participants enrolled. The conditions listed are hyperphosphatemia and end-stage renal disease. The recorded start is 2008-03, and primary completion is 2009-01.
The study is recorded as single-group, with no masking and allocation listed as NA. Participants were to switch from their current phosphate binder to ferric citrate and be titrated to the maximum tolerated dose, up to about 12g/day, based on serum phosphorus.
The primary outcome is the difference in mean serum phosphorus between baseline (Day 0) and the end of treatment (Day 28), measured in mg/dL. The numerical result and its analysis are not reported in the registry record. Safety entries list 4 of 55 participants affected by serious adverse events and 46 of 55 affected by other adverse events. Deaths are not reported in the registry record.