Effects of Lanthanum Carbonate on FGF-23 in Subjects With Stage 3 CKD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Lanthanum Carbonate on FGF-23 in Subjects With Stage 3 CKD (NCT01128179), a randomized phase 2 study. The primary outcome is Natural Logarithm Transformed Serum Intact Fibroblast Growth Factor (FGF-23) Levels at Week 12 Last Observation Carried Forward (LOCF).

2. Clinical Question

The clinical question concerns a biomarker involved in mineral metabolism, not a direct measure of symptoms, kidney function, or another patient-centered outcome. The registry description says FGF-23 is secreted by bone cells in response to hyperphosphatemia and acts to decrease renal phosphate reabsorption. It also states that a reduction in FGF-23 was expected with administration of a phosphate binder. That expectation describes the study rationale; it is not itself evidence that the observed results met the expectation.

The comparison is between assigned treatment groups, while the primary result is reported for the per-protocol population. The population definition therefore matters when interpreting the finding: it excludes participants who did not meet the stated data-availability and protocol-deviation criteria. The registry record does not report the full reasons that participants were excluded from this analysis.

3. Trial Design

The registry describes a completed phase 2a, randomized, double-blind, parallel-group, placebo-controlled study sponsored by Shire. The enrollment was 35. The recorded start date was 2010-12-06, and the primary completion date was 2012-04-16. The study involved subjects with chronic kidney disease, with the official title specifying normo-phosphataemic subjects with stage 3 chronic kidney disease.

Participants were assigned to lanthanum carbonate or placebo. The primary outcome was assessed at 12 weeks, using the last observation carried forward (LOCF) approach where applicable. The primary analysis population was the per-protocol set rather than all enrolled participants. In the posted primary outcome results, the arm sizes are 17 for lanthanum carbonate and 12 for placebo. These are the numbers included in that outcome analysis and should not be treated as the total enrollment.

The registry lists six secondary outcomes, including changes in parathyroid hormone, vitamin D, urinary fractional excretion of phosphate, serum phosphate, total calcium, and calcium-phosphate product. Results are posted for only some of those outcomes in the record; the status of unreported results is not established by the posted information.

The registry record does not report the original sample-size justification, allocation ratio details beyond the randomized parallel-group design, the randomization sequence method, concealment procedures, or the treatment dose and administration schedule. It also does not report whether interim analyses were planned or conducted. Those details should not be inferred from the phase, trial design, or small enrollment. The record identifies double masking but does not specify which roles were masked.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-protocol (PP) set are subjects who received at least 1 dose of investigational product and who had primary data assessment available from Week 2 or later and who did not have pre-defined major protocol deviations that could have affected the primary variable.

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: The Safety Analysis Set was defined as all randomized subjects who received at least 1 dose of investigational product. This population was used in all safety reporting.

6. Primary Endpoint

The registry lists the primary outcome as Natural Logarithm Transformed Serum Intact Fibroblast Growth Factor (FGF-23) Levels at Week 12 Last Observation Carried Forward (LOCF), measured over 12 Weeks.

The primary endpoint was natural-log-transformed serum intact Fibroblast Growth Factor 23 (FGF-23) levels at week 12, using last observation carried forward. FGF-23 is a biomarker connected with phosphate regulation in chronic kidney disease. The registry description says it is secreted by bone cells in response to hyperphosphatemia and decreases renal phosphate reabsorption. Measuring it offered a way to examine a biological response to the phosphate binder in this proof-of-concept study.

The logarithmic transformation means that the analysis concerns transformed values rather than a direct comparison of the raw concentration scale. The registry reports least-squares means and their standard errors for the primary endpoint. It does not report the exact transformation procedure beyond identifying the natural logarithm, nor does it provide a clinical threshold for a meaningful change in FGF-23. The reported unit is pg/ml, but the outcome is explicitly described as natural-log-transformed.

The endpoint is a biomarker measure, not a clinical event or a direct measure of how participants feel or function. A difference in this outcome, if observed, would address the trial’s stated biological question; by itself it would not establish a difference in other outcomes or clinical benefit. The record lists additional mineral-metabolism measures as secondary outcomes, but they do not replace the primary endpoint or answer the same question.

7. Results Posted in the Registry

• Lanthanum Carbonate: mean 4.01 versus 4.12 on control; difference -0.11 (95% CI -0.33 to 0.10), standardized effect d = -0.38; z-test p = 0.309.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Serum Intact Parathyroid Hormone (iPTH) Values at Week 12 (LOCF)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Lanthanum Carbonate: mean 1.67 versus -4.87 on control; difference 6.54 (95% CI -5.54 to 18.62), standardized effect d = 0.40; z-test p = 0.288.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Lanthanum Carbonate and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in 1,25-Dihydroxy Vitamin D Values at Week 12 (LOCF)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Lanthanum Carbonate: mean -1.75 versus -6.86 on control; difference 5.11 (95% CI -4.73 to 14.95), standardized effect d = 0.38; z-test p = 0.309.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Lanthanum Carbonate and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Urinary Fractional Excretion of Phosphate Values at Week 12 (LOCF)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Lanthanum Carbonate: mean -5.90 versus -2.20 on control; difference -3.70 (95% CI -8.44 to 1.04), standardized effect d = -0.58; z-test p = 0.126.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Lanthanum Carbonate and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists six secondary outcomes, while results are posted for three in the record described. These include measures related to parathyroid hormone, vitamin D, and urinary phosphate handling. The estimates vary in direction and uncertainty. Their intervals include zero, and the posted unadjusted comparisons do not show a clearly separated pattern of group differences. The secondary results therefore add descriptive context but do not form a consistent body of confirmatory evidence that changes the reading of the primary endpoint.

These measures concern other aspects of mineral metabolism and are biologically related to the primary biomarker question, but they are distinct outcomes. They cannot be treated as interchangeable with FGF-23 or as independent confirmation of the primary result. The primary endpoint remains the stated main focus of the study. The secondary results do not resolve the uncertainty in the primary estimate.

Unadjusted secondary p-values carry less weight when several outcomes are examined because the chance of obtaining a seemingly notable result can increase across multiple comparisons. This is a general statistical concern, not a claim about the actual probability of a false positive in this trial. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for the secondary outcomes. The secondary findings should consequently be read as exploratory, with attention to effect estimates and uncertainty rather than isolated p-values.

Results for the other listed secondary outcomes are not reported in the registry record. Their absence from the posted results means their direction and precision cannot be assessed from this record. It would be inappropriate to infer that they were not measured, or to infer their findings from the outcomes that are posted.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline in Serum Intact Parathyroid Hormone (iPTH) Values at Week 12 (LOCF)
• Change From Baseline in 1,25-Dihydroxy Vitamin D Values at Week 12 (LOCF)
• Change From Baseline in Urinary Fractional Excretion of Phosphate Values at Week 12 (LOCF)
• Change From Baseline in Serum Phosphate Values at Week 12 (LOCF)
• Change From Baseline in Serum Total Calcium Values at Week 12 (LOCF)
• Change From Baseline in Calcium-Phosphate Product Values at Week 12 (LOCF)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical measurement of transformed FGF-23 rather than a count, binary event, or time until an event. The registry reports least-squares means for each group, alongside standard errors. A least-squares mean is a model-based group mean; it need not be identical to a simple arithmetic average. The record identifies the sponsor’s primary comparison method as ANCOVA, but does not report the covariates used in that model or enough detail to reconstruct its adjusted estimate.

What does the recalculation represent?

The recalculated comparison uses the posted group summaries to form a simple, unadjusted mean difference. It is not the sponsor’s ANCOVA and does not incorporate any covariate adjustment. Its confidence interval and unadjusted p-value are useful as a transparent summary-statistic comparison, but they should be distinguished from the registry’s reported analysis. For the primary result, the sponsor’s estimate is close to the recalculated estimate at the displayed precision, while the interval and p-value are not identical. The two analyses answer closely related but not identical statistical questions because their procedures differ.

The recalculation describes a difference between the lanthanum carbonate and placebo group means on the reported endpoint scale. A negative difference means the lanthanum carbonate group’s estimated mean is lower than the placebo group’s estimate in this coding of the contrast. That direction alone does not establish whether the difference is important, reliable, or attributable to treatment. Interpretation requires the uncertainty interval, the analysis population, and the endpoint definition.

How should the confidence interval and p-value be read?

A confidence interval conveys uncertainty about the estimated contrast. In general, it describes a range of values compatible with the data and the statistical procedure, under the model’s assumptions. When an interval includes zero for a difference, the data are compatible with no group difference as well as with differences in either direction. That does not mean every value in the interval is equally plausible, nor does it establish that the groups are equivalent.

A p-value measures how unusual the observed data, or data more extreme, would be under a specified null hypothesis and the analysis assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The posted primary p-values do not provide strong evidence against a no-difference null under the reported analyses. They also do not demonstrate that no effect exists. The registry record does not report a decision threshold for clinical importance.

Why can the recalculated and sponsor results differ?

ANCOVA can adjust a comparison for baseline or other covariates included in its model, whereas the recalculation is unadjusted. Adjustment can affect the estimate’s uncertainty and, depending on the model, its point estimate. The registry record does not identify the ANCOVA covariates or provide the participant-level data needed to reproduce that analysis. The differences between the posted sponsor interval and the recalculated interval therefore should not be interpreted as a calculation error based on the available record. The sponsor analysis remains the reported trial analysis; the recalculation is a separate descriptive check.

The arm-level spread is reported as a standard error, not as a standard deviation. Standard errors describe uncertainty in estimated means and depend on the amount of information contributing to those estimates. They are not measures of the variation among individual participants. Where a recalculation uses an approximate standard deviation inferred from summary information, it remains an approximation and not a participant-level reconstruction. General statistical point: a larger standard error indicates less precise estimation of the corresponding mean, all else equal.

What does the analysis population mean?

The primary endpoint uses the per-protocol set, defined in the registry as participants who received at least one dose, had a primary data assessment from week 2 or later, and had no predefined major protocol deviations that could have affected the primary variable. This is narrower than an analysis of all randomized participants. The record does not report the full set of exclusions, the number randomized to each group, or a separate intention-to-treat estimate. The listed enrollment should therefore not be assumed to be the denominator for the primary result.

The endpoint also uses last observation carried forward. In general, LOCF substitutes a participant’s last observed measurement for a later missing measurement. This approach relies on assumptions about what the unobserved later value would have been; it does not recover the missing outcome. The registry record does not report how many values were carried forward, the amount or pattern of missingness, or sensitivity analyses using alternative missing-data approaches. Consequently, the potential influence of this method cannot be assessed from the posted information.

Why does over-dispersion matter in general?

For continuous outcomes, variability among individual measurements affects how precisely a group difference can be estimated. General statistical explanation: if a model understates the actual variability, its standard errors may be too small and its intervals too narrow; if it overstates variability, precision can be understated. The registry gives standard errors for the group means but does not provide participant-level distributions or diagnostics to assess the shape of the outcome data. Since the primary outcome is transformed, the results should be understood on that transformed scale rather than converted informally to the raw scale.

Finally, the registry does not report the prespecified statistical analysis plan, details of covariate selection, interim analyses, or a multiplicity strategy. These omissions limit assessment of whether the posted analyses fully match the original plan. They do not invalidate the reported figures, but they constrain how confidently their analytical context can be evaluated.

11. Confidence Intervals and Precision

The primary recalculated interval runs from a negative to a positive value, as does the sponsor-reported 95% interval. In both cases, zero lies within the interval. This means the data are compatible with no difference as well as with a range of differences in either direction. The interval is not evidence that the true difference is exactly zero, and it does not establish equivalence between treatment groups.

Precision concerns the breadth of plausible values around an estimate, not whether the result is statistically significant in isolation. The primary per-protocol comparison includes 17 participants in the lanthanum carbonate group and 12 in the placebo group. These arm sizes help explain why the estimate may remain uncertain, although the registry record does not give a precision target or a prespecified clinically important difference for FGF-23.

The sponsor’s ANCOVA estimate and recalculated estimate are close at the displayed precision, but their confidence intervals are not identical. That difference reflects the distinction between the sponsor’s model-based analysis and the unadjusted recalculation. The sponsor analysis is the trial’s reported analysis; the recalculated interval is not a substitute for it.

Confidence intervals are conditional on the statistical method and its assumptions. The registry does not provide enough detail to assess the ANCOVA covariates, the distribution of individual transformed values, or the sensitivity of the findings to missing-data assumptions. It also does not report an equivalence margin. Thus, the interval can describe statistical uncertainty around the estimated difference, but it cannot by itself establish clinical importance, exclude all meaningful effects, or resolve the limitations of the analysis population.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect in this trial, not the original design justification. For these continuous outcomes, the figures are participants per arm, not total events. The calculation assumptions listed in the registry record are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm that the planning calculation would require to have an 80% chance of detecting the selected effect under its assumptions, if that effect were present. The 90% power column gives the corresponding planning number for a 90% chance. These are prospective design illustrations. They are not estimates of the probability that the completed trial detected an effect, and they do not tell whether the observed finding is true. This is not observed power.

Rows for 100%, 75%, and 50% of the observed effect show how the assumed target effect changes the planning requirement. Smaller effects require more participants because they are harder to distinguish from random variation. For the primary contrast, the illustration gives 107 participants per arm at 100% of the observed effect, 190 at 75%, and 428 at 50% for 80% power. For 90% power, the corresponding listed figures are 143, 255, and 572 participants per arm.

These values are sensitive to the observed effect used as the planning basis, as well as the stated assumptions. Because the observed effect in a small study can be imprecise, the illustrations should not be treated as a definitive recommendation for a future study. The registry record does not report the trial’s original planning rationale, so these calculations should remain distinct from the design decisions made for this trial.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.112; pooled standard deviation σ = 0.292.
2. n = 2 × (1.96 + 0.842)² × 0.292² / -0.112² = 106.8, rounded up to 107 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.112100000000001                      # observed difference in means
sigma <- 0.292345295587002                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1128179)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 107 (80% power), 143 (90% power)
 75% of observed effect: n per arm = 190 (80% power), 255 (90% power)
 50% of observed effect: n per arm = 428 (80% power), 572 (90% power)
power.t.test: 107.7 
Simulated power at n = 107 per arm: 0.795 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as an ANCOVA analysis of final values. The sponsor estimate is the same as the recalculated estimate at the displayed precision, but the confidence interval and p-value differ. The sponsor reports a 95% confidence interval that extends from a negative value to a positive value and a p-value of 0.319. The unadjusted recalculation also has an interval that includes zero and an unadjusted p-value of 0.309.

The recalculation is based on posted summary statistics and is not the sponsor’s ANCOVA. It is therefore a simple unadjusted comparison, not an attempt to reproduce the trial’s model-based analysis. ANCOVA may account for covariates that are not reflected in the summary-statistic calculation. The registry record does not report which covariates were included, preventing a full reconstruction of the sponsor analysis.

The sponsor analysis should be treated as the principal reported trial result; the recalculation provides a secondary check on the posted summary data. Both analyses give an uncertain estimate whose interval includes no difference. Their agreement in direction and displayed point estimate does not remove the uncertainty, and their differing intervals and p-values should not be collapsed into one result. The registry record does not flag a discrepancy between sponsor and recalculated results.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and six secondary outcomes. Considering several outcomes raises a multiplicity question: if each is tested separately, the overall chance of at least one apparently notable result can be higher than for a single prespecified test. General statistical practice may address this through adjustment procedures or a defined testing hierarchy. The registry record does not report whether either approach was prespecified or used. The posted secondary p-values should therefore be considered unadjusted unless the record states otherwise.

Several details needed to evaluate the analysis plan are not reported in the registry record. These include the original sample-size justification, the full statistical analysis plan, the covariates used in the sponsor’s ANCOVA, whether interim analyses were planned or conducted, and any multiplicity procedure. The record also does not establish which analyses were prespecified and which may have been exploratory. These gaps limit assessment of how closely the reported analyses follow the original plan.

The primary endpoint uses LOCF and a per-protocol population. The per-protocol definition is given, but the record does not report the number or reasons for exclusions from that population, a parallel intention-to-treat result, or sensitivity analyses for missing outcomes. It does not report how often LOCF was applied or the pattern of missing data. General statistical explanation: carrying a last measurement forward assumes that this carried value is a suitable stand-in for the unavailable later measurement; that assumption may not hold in every setting.

These omissions do not prove that the analyses were inappropriate. They mean that readers cannot fully evaluate missing-data sensitivity, analysis-population robustness, or multiplicity control from the registry record. In particular, the results should not be treated as a comprehensive account of every planned endpoint because results for some listed secondary outcomes are not reported in the registry record.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac failure (4.3%), myocardial ischemia (4.3%), pancreatitis acute (4.3%).

For serious adverse events, the registry reports 23 participants at risk in the lanthanum carbonate group, with 2 affected, and 12 at risk in the placebo group, with 0 affected. These are descriptive counts within the posted safety groups. They do not, on their own, establish that treatment caused or prevented an event. The record reports no death counts; deaths are not reported in the registry record.

The listed serious-event terms are cardiac failure, myocardial ischemia, and acute pancreatitis, each shown as 4.3%. The record does not establish from these term listings whether the same participant could contribute to more than one term, so the terms should not be added or treated as a count of distinct participants. The figures are not a complete description of all possible harms, and the small safety-group sizes make the counts imprecise.

The registry also records other adverse events in the same risk groups: 2 affected in the lanthanum carbonate group and 0 in the placebo group. Serious and other adverse-event summaries are descriptive safety information. They should be interpreted alongside the trial’s short 12-week period and limited enrollment, without inferring causality from a difference in counts.

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

The primary result is an estimate of the difference in natural-log-transformed serum intact FGF-23 at week 12 between the randomized groups in the per-protocol analysis. The reported group means and the comparison provide a quantitative account of the biomarker contrast in the participants included in that analysis. The uncertainty interval includes zero, so the posted results do not clearly separate the groups on this measure.

This does not show that the groups are equivalent or that there was no possible effect. A result that is not statistically distinguishable from zero can reflect a genuinely small difference, substantial uncertainty, or both. The registry does not state an equivalence margin or a clinically important threshold for FGF-23. The evidence therefore cannot be used to decide from this record alone whether any estimated difference would matter clinically.

The outcome is a biomarker rather than a clinical event, symptom, or direct measure of kidney function. Even a precise change in this endpoint would not by itself establish an effect on other outcomes. The posted secondary measures broaden the description of mineral metabolism, but their unadjusted nature and the absence of reported multiplicity procedures limit confirmatory interpretation.

The study is identified as a proof-of-concept phase 2a trial, with enrollment of 35 and a primary per-protocol analysis involving 17 participants in the lanthanum carbonate arm and 12 in the placebo arm. The short outcome timeframe and analysis population are relevant to generalizability. The record does not provide detailed information about the participants’ broader clinical characteristics, treatment dose, or longer-term follow-up, so conclusions beyond the defined population and period are not supported.

The appropriate reading is narrow: the registry reports an uncertain estimate for a biological endpoint under the specified analysis. It neither establishes a clinically meaningful benefit nor proves the absence of an effect. The result should not be extended to unreported outcomes, populations, treatment schedules, or longer time periods.

18. Why This Trial Matters Statistically

This trial illustrates why a point estimate and its uncertainty need to be read together. The primary contrast is directionally below zero for lanthanum carbonate versus placebo, but the confidence interval spans zero. Looking only at the direction or the p-value would miss how much uncertainty remains about the size and direction of the difference.

It also shows the distinction between an analysis reported by the sponsor and a simple recalculation from summary statistics. The registry’s ANCOVA result is the trial’s own reported comparison, while the unadjusted recalculation is a separate check. Their close point estimates do not make their methods interchangeable, and the available registry entries are insufficient to reproduce the ANCOVA.

The sample-size illustrations highlight the dependence of planning on the effect size a future study aims to detect. The planning figures increase when the target is a smaller fraction of the observed effect. These calculations are not evidence about the probability that this completed trial found a real effect, and the registry does not report its original sample-size justification.

Finally, the per-protocol population, LOCF method, multiple secondary outcomes, and incomplete reporting of analysis details are central statistical context, not technical footnotes. They shape how far the biomarker findings can be interpreted and reinforce the need to distinguish an exploratory proof-of-concept result from definitive evidence about clinical outcomes.

19. 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 primary analysis uses the per-protocol set, which is narrower than all randomized participants. Although the registry defines this set, it does not report the reasons for each exclusion or a complementary intention-to-treat estimate. This limits assessment of whether the primary result is sensitive to the analysis population. The enrollment is 35, while the posted primary arm sizes are 17 and 12; the record does not reconcile these figures participant by participant.

The primary endpoint uses last observation carried forward. The number of carried-forward observations, the pattern of missingness, and sensitivity analyses are not reported in the registry record. The effect of this missing-data approach on the result therefore cannot be judged from the posted information. The original analysis plan, ANCOVA covariates, and any interim analyses are also not reported.

The study assessed a biomarker at 12 weeks, and the record does not report a clinical threshold for a meaningful FGF-23 change. The posted result cannot directly establish effects on clinical outcomes or longer-term measures. The official title identifies a normo-phosphataemic stage 3 CKD population, but further participant characteristics needed to assess applicability are not reported in the registry record.

The registry lists six secondary outcomes, but results are posted for only some of them. It does not report a multiplicity strategy, which limits the confirmatory interpretation of multiple secondary comparisons. Safety counts are also based on limited groups and should be treated as descriptive; death counts are not reported in the registry record. These limitations do not negate the posted estimates, but they constrain their precision, reproducibility, and scope.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Effects of Lanthanum Carbonate on FGF-23 in Subjects With Stage 3 CKD — NCT01128179.
• Registry record last updated 2021-06-09; status last verified 2021-05.
• Results first posted 2013-05-22.
• 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.

23. Record Summary

The registry describes a completed, randomized, double-blind, parallel-group, placebo-controlled phase 2a study of lanthanum carbonate in subjects with stage 3 chronic kidney disease. Enrollment was 35. The study assessed serum intact FGF-23 after 12 weeks, with the primary analysis conducted in a per-protocol population and using last observation carried forward.

The primary sponsor-reported ANCOVA estimate and the unadjusted recalculation point in the same direction, while both reported intervals include zero. The result is therefore uncertain and does not establish a difference or equivalence. The registry lists six secondary outcomes, with only some results posted, and reports descriptive serious adverse-event counts. Details of the original sample-size justification, multiplicity plan, missing-data sensitivity analyses, and several analysis procedures are not reported in the registry record.