Safety and Efficacy Study for AKB-6548 in Participants With Chronic Kidney Disease and Anemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study for AKB-6548 in Participants With Chronic Kidney Disease and Anemia (NCT01235936), a na phase 2 study. The primary outcome is Mean Change From Baseline in Hemoglobin (Hgb) on Day 29.

2. Clinical Question

The clinical question is descriptive rather than a comparison between randomized groups. Participants received the study drug, and the primary outcome concerns how hemoglobin measurements at Day 29 differed from their defined baseline. Without a concurrent control group, a change over time cannot by itself separate a treatment-associated change from other explanations, such as natural variation, changes in participants’ circumstances, or measurement variability.

The baseline definition is specific: it is the average of the two samples obtained before dosing, identified as Pre-Baseline and Baseline. The endpoint is therefore a comparison of a later measurement with that two-sample baseline value, not a comparison with another group. The record says that a positive change indicates increased hemoglobin concentration.

The registry identifies anemia and kidney disease as the conditions of interest and describes participants as having anemia secondary to chronic kidney disease. It does not report further eligibility details in the record, nor does it provide a numerical estimate of the primary outcome. The clinical question can therefore be described from the registered design and endpoint, but the size and precision of the observed hemoglobin change cannot be assessed from the posted information.

3. Trial Design

This was a Phase 2a open-label pilot study of repeat oral doses of AKB-6548 in participants with anemia secondary to chronic kidney disease. The official title describes a 28-day dosing period and participants with chronic kidney disease stages 3 and/or 4. The brief summary describes the participants as pre-dialysis. The record lists a single-group model, no masking, and allocation as not applicable; it does not describe a randomized comparison or a separate control group.

The enrollment was 10. The study is marked completed. Its recorded start date is 2010-10-21, and its primary completion date is 2011-04-13. These administrative dates describe the registered study timeline; they do not establish how long each participant was followed beyond what is explicitly stated for the outcomes.

The stated purpose was to evaluate safety, pharmacodynamics, and pharmacokinetics of repeat oral doses. The primary outcome was mean change from baseline in hemoglobin on Day 29. The record also lists secondary outcomes involving hematocrit, total red blood cell count, absolute reticulocyte count, reticulocyte hemoglobin content, and participant counts for specified changes in hemoglobin, hematocrit, and red blood cell count. The total number of outcome measures is listed as 20, while the record also lists 9 analyses. Numerical results for the primary endpoint are not reported in the registry record.

The primary outcome population is described as the Full Analysis Set, defined as all participants who received at least 1 dose of study medication. Its population description also says that results were summarized as a single treatment arm and that no separate analysis by disease state was performed. The same description refers to participants receiving Vadadustat, whereas the intervention is named AKB-6548 elsewhere in the record. That naming difference is present in the registry information; its explanation is not reported in the registry record.

Because the study has one group and is open-label, its design can describe measurements and safety events observed among treated participants, but does not supply a randomized, masked treatment contrast. The registry record does not report a protocol rationale for the design, a sample-size justification, or details of any interim analyses.

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 enrolled Chronic Kidney Disease (CKD) Stage 3 or CKD Stage 4 participants. Per protocol, this is a pilot study and all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state as the Sponsor terminated the study early after enrolling 10 participants.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: All participants who received at least 1 dose of study medication. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

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: Full Analysis Set: All participants who received at least 1 dose of study medication. Per the protocol, all results data are summarized as a single treatment arm (i.e., all participants receiving Vadadustat); no separate analysis was performed to report results by disease state.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in Hemoglobin (Hgb) on Day 29, measured over Baseline; Day 29.

The primary endpoint is mean change from baseline in hemoglobin (Hgb) on Day 29, measured in grams per decilitre (g/dL). Hemoglobin is the blood measurement identified by the registry as the primary outcome. The outcome is expressed as a change, so its interpretation depends on both the baseline definition and the Day 29 measurement.

Baseline is defined as the average of two samples obtained before dosing: Pre-Baseline and Baseline. The registry states that a positive change from baseline indicates an increase in hemoglobin concentration. It specifies the mean as the summary measure and standard deviation as the measure of dispersion. The numerical mean change and standard deviation are not reported in the registry record.

In general, a mean change condenses participants’ individual changes into an average. It can communicate the direction and central tendency of the observed measurements, but it does not show how similar or different individual participants’ changes were. A standard deviation describes variation among observations around the mean; it is not the same as a confidence interval and does not, by itself, show the precision of the estimated mean.

Repeated blood measurements before dosing can provide a defined reference point for assessing change, while the Day 29 outcome describes the measurement at the specified endpoint. The registry lists several additional blood-count outcomes, but they do not replace the prespecified primary outcome. Since the numerical primary result is not reported in the registry record, its magnitude, variability, and precision cannot be evaluated from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized as a mean, with standard deviation as its dispersion measure. The endpoint is mean change from baseline in hemoglobin on Day 29. This identifies the kind of quantity the analysis was intended to summarize, but it does not give the result itself: the numerical mean change and standard deviation are not reported in the registry record.

What does a mean change represent?

In general, a change score is calculated for each participant by comparing a measurement at follow-up with a baseline measurement. A mean change then summarizes those participant-level changes. It is different from reporting only the average follow-up value, because the change score incorporates a reference measurement for each participant. The registry specifies that baseline is the average of the Pre-Baseline and Baseline samples collected before dosing. It also states that a positive change indicates an increase in hemoglobin concentration.

In general, the mean is useful for describing the central tendency of a continuous measurement, but it can conceal differences between participants. A few large changes can influence an average, and the same mean can arise from quite different patterns of individual responses. The standard deviation describes the spread of the observations around the mean. It does not indicate whether the average is estimated precisely; precision depends on the variability and amount of information available and is ordinarily communicated using an uncertainty interval.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical model and confidence procedure. A narrower interval indicates greater precision than a wider interval, while neither width nor location alone establishes clinical importance. A hypothesis test and its p-value address a different question: how compatible the data are with a specified null model, subject to the assumptions and analysis choices. The registry information does not report a confidence interval or p-value for the primary endpoint, and it does not identify a numerical effect estimate.

A standard deviation should not be mistaken for a confidence interval. The former describes dispersion among participant measurements; the latter represents uncertainty about an estimated quantity. Likewise, a mean change does not reveal each participant’s response. Without the numerical endpoint result and its accompanying dispersion or uncertainty information, it is not possible to judge the observed variation or precision.

What does the single-group design permit?

In general, a single-group study can describe outcomes observed after participants receive an intervention. A change from baseline can be informative as a within-group description, but it is not a randomized treatment effect. A control group would help estimate how outcomes might change over the same period without the intervention. Here, the registry identifies a single-group model, no masking, and allocation as not applicable. It does not identify a concurrent control group.

Consequently, even if a numerical change were available, the design alone would not distinguish an intervention-associated change from other influences over time. This is a design limitation, not a calculation problem. Statistical adjustment cannot create a randomized comparator that the design does not contain. The registry record does not report an adjusted comparative analysis.

What do the planning assumptions mean?

The record includes a description of sample-size planning illustrations based on an observed effect. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, such planning quantities are described as participants per arm. These are planning illustrations, not observed enrollment or observed power. The numerical illustration values are not included in the information.

In general, a planning calculation asks how much information a future study might need under stated assumptions. Its result depends on the effect size used, the assumed variability, allocation, significance level, and power target. If the assumed effect is based on an observed effect from a small pilot, that estimate can be unstable. A planning illustration cannot demonstrate that the pilot itself had a particular probability of detecting an effect. The registry record does not report the trial’s own sample-size justification or explain whether these illustrations were part of the original design.

Why does over-dispersion matter in general?

For outcomes analyzed as counts, a statistical model may assume a particular relationship between the mean and variance. Over-dispersion means that the observed variability exceeds what that model expects. If it is ignored, standard errors can be too small and uncertainty can appear understated. This is a general issue for count outcomes; it should not be assumed to apply to this study’s continuous primary endpoint. The registry information does not identify an over-dispersion adjustment or describe a count-model analysis.

The reported endpoint is continuous, so its stated summary is a mean and standard deviation. The record does not specify additional model details, transformation choices, covariate adjustments, confidence-interval methods, or handling of unusual values. Those analysis details are not reported in the registry record. General methods can clarify what the named summaries mean, but cannot fill in unreported analysis procedures.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures and 9 analyses. The primary outcome is mean change from baseline in hemoglobin on Day 29, and the record also names secondary outcomes involving hematocrit, red blood cell counts, reticulocyte measures, and counts of participants meeting specified change descriptions. The numerical findings for these outcomes are not reported in the registry record.

In general, multiplicity arises when multiple outcomes, time points, subgroups, or statistical tests are examined. If each is treated as a separate opportunity to find evidence without an appropriate plan for interpretation, the chance of at least one apparently notable result can increase. Methods for addressing multiplicity may include defining a primary endpoint, ordering tests, or adjusting inference. Which outcomes were designated as confirmatory, whether any adjustment was planned, and whether a multiplicity procedure was used are not reported in the registry record.

The primary population is described as the Full Analysis Set, consisting of all participants who received at least 1 dose of study medication. This definition indicates who was intended to contribute to the analysis, but the record does not report the number with an available Day 29 measurement, the amount or reasons for missing data, or how missing endpoint values were handled. The treatment of participants who discontinued or had incomplete measurements is not reported in the registry record.

In general, missing data can affect both the estimate and its uncertainty, depending on how much information is missing and why it is missing. Complete-case analysis, imputation, and model-based approaches rely on different assumptions. Without a description of the missing-data pattern and analysis method, the robustness of an endpoint estimate cannot be assessed. The record also does not report sensitivity analyses for missing data.

The population description states that results were summarized as a single treatment arm, with no separate analysis by disease state. A subgroup analysis plan, if any, is not reported in the registry record. These omissions limit the ability to determine exactly how the analyses were conducted and how much confidence to place in any outcome-specific finding.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event entry identifies a group titled Vadadustat. It records 10 participants at risk for serious adverse events, with 0 affected. For other adverse events, it records 10 participants at risk and 5 affected. The recorded death count is 0. No top serious adverse-event terms are listed.

These are participant counts in the registry record, not event rates calculated for a comparison between groups. The study has one treatment group and no concurrent control group, so the figures do not estimate a difference in safety outcomes between treatments. They also do not describe the timing, duration, severity, or outcome of the other adverse events. The identity of the listed adverse-event group differs in name from the intervention entry, which lists AKB-6548; the reason is not reported in the registry record.

In general, a zero count in a small study does not demonstrate that an event cannot occur. It indicates that no affected participants are recorded for that category in the registry entry. The enrollment was 10, so the safety observations come from a limited group; the record does not provide enough information to characterize uncommon events reliably or to compare risks with another group.

The counts should therefore be read as a registry description of recorded events during the study, not as proof of overall safety or absence of risk. Further details about event definitions, collection procedures, attribution, and follow-up are not reported in the registry record.

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

The record establishes that this was a completed Phase 2a, open-label, single-group pilot study of repeat oral AKB-6548 in participants described as having anemia secondary to chronic kidney disease. It identifies mean change from baseline in hemoglobin on Day 29 as the primary outcome and specifies how baseline was defined. It also lists additional blood-count outcomes and safety measures.

Those design details do not establish the observed treatment result. The numerical primary mean change, its standard deviation, and any confidence interval or hypothesis-test result are not reported in the registry record. It is therefore not possible to state how large the average change was, in which direction it went, or how precisely it was estimated. Listing secondary outcomes does not establish their results either.

Even with a reported within-group change, this design would describe change among participants rather than isolate a causal effect. There was no concurrent comparator group, and the study was open-label. In general, change from baseline can reflect the intervention and other influences over time, and a single-group study cannot directly show what would have happened under a different treatment or without treatment.

The adverse-event entry records 0 participants with serious adverse events, 5 with other adverse events, and 0 deaths, among 10 participants at risk for each event category. These counts should be understood as limited observations in a small single-group study. They do not establish that serious events cannot occur, and they do not provide a comparative safety estimate.

The record’s primary population description refers to participants receiving Vadadustat, while the intervention is named AKB-6548. The explanation for this naming difference is not reported in the registry record. Overall, the registered information is sufficient to describe the study’s purpose, structure, and endpoint definitions, but not to assess the numerical efficacy result or its precision.

13. Why This Trial Matters Statistically

This trial is statistically useful as an example of how a pilot study can define a measurable outcome while leaving important questions unresolved in the registered results. The primary outcome is clearly named as mean change from baseline in hemoglobin on Day 29, and the baseline is specified as the average of two pre-dose samples. These details matter because interpretation of a change score depends on what counts as baseline and when the follow-up measurement was taken.

The single-group, open-label structure also illustrates the difference between describing change and estimating a comparative treatment effect. A within-group change can summarize what was observed in participants, but without a control group it does not establish how outcomes would have changed in the absence of the intervention. That distinction remains important even when an endpoint is objective and measured in blood samples.

The record describes a pilot with enrollment of 10 and lists multiple outcomes. In general, pilot studies can help describe procedures and generate estimates for later planning, but small studies often provide limited precision. A planning illustration based on an observed effect is not the same as observed power, and it depends on its assumptions. The registry record does not report its own sample-size justification or the numerical results needed to evaluate the stated endpoint.

Finally, the record demonstrates why completeness and consistency of reporting matter. The intervention is named AKB-6548 in one place, while the population and adverse-event descriptions use Vadadustat. The reason for this naming difference is not reported in the registry record. Missing numerical endpoint findings, analysis details, and missing-data information further limit interpretation. Statistical design can be described from the record, but conclusions about the measured effect require results and uncertainty estimates.

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 direct limitation for interpreting the primary outcome is that its numerical result is not reported in the registry information. The mean change, standard deviation, and any uncertainty interval or test result are absent, so the direction, magnitude, and precision of the endpoint cannot be assessed.

The study is described as open-label and single-group, with allocation not applicable. It therefore does not provide a randomized control comparison. A change from baseline, even if numerically reported, would not by itself identify the change attributable to the intervention. The registry record does not describe an adjusted comparative analysis.

Enrollment was 10, limiting the amount of information available for evaluating variability and safety. The adverse-event counts are recorded for 10 participants at risk, but the registry information does not give event timing, duration, attribution, or detailed descriptions of the other adverse events. A zero serious-event count in this group cannot establish that such events are impossible or that risk is absent.

The record lists 20 outcome measures and 9 analyses, but does not report the numerical findings or explain the statistical plan for interpreting multiple outcomes. Multiplicity handling, missing-data methods, and the number of participants with observed Day 29 measurements are not reported in the registry record. The record also does not report interim-analysis procedures or the study’s sample-size justification.

There is a naming difference between the intervention entry, AKB-6548, and references to Vadadustat in the primary population description and adverse-event group. Its explanation is not reported in the registry record. This makes it important to avoid silently treating the labels as interchangeable when interpreting the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy Study for AKB-6548 in Participants With Chronic Kidney Disease and Anemia — NCT01235936.
• Registry record last updated 2022-07-01; status last verified 2022-06.
• Results first posted 2022-07-01.
• 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 2a, open-label, single-group pilot study of repeat oral AKB-6548 in pre-dialysis participants with anemia secondary to chronic kidney disease. The official title specifies stages 3 and/or 4 and a 28-day dosing period. Enrollment was 10; the recorded start date was 2010-10-21, and primary completion was 2011-04-13.

The primary outcome was mean change from baseline in hemoglobin on Day 29. Baseline was defined as the average of the Pre-Baseline and Baseline samples, and a positive change indicates increased hemoglobin concentration. The numerical primary result and its variability are not reported in the registry record.

The adverse-event entry records 0 serious adverse events among 10 at risk, 5 participants with other adverse events among 10 at risk, and 0 deaths. The intervention and some outcome-population descriptions use different drug names; the reason is not reported in the registry record.