A Study to Assess the Pharmacokinetics of Lanthanum Carbonate, Investigate and Compare the Efficacy, Safety and Tolerability of Lanthanum Carbonate With Calcium Carbonate in Hyperphosphataemic Children and Adolescents With Chronic Kidney Disease on Dialysis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Pharmacokinetics of Lanthanum Carbonate, Investigate and Compare the Efficacy, Safety and Tolerability of Lanthanum Carbonate With Calcium Carbonate in Hyperphosphataemic Children and Adolescents With Chronic Kidney Disease on Dialysis (NCT01696279), a non-randomized phase 2 study. The primary outcome is Percentage of Participants Achieving Age-Specific Kidney Disease Outcomes Quality Initiative (KDOQI) Targets for Serum Phosphate Level Following 8 Weeks of Lanthanum Carbonate Administration (Part 2 + Part 3).

2. Clinical Question

The question is about target attainment, a binary outcome: each eligible participant either meets the specified threshold or does not. It is not the same as asking how much serum phosphorus changed on average. A target-based measure can describe whether participants reached a clinically defined range, while a change measure describes movement from an earlier measurement. The record also lists secondary outcomes concerning serum phosphorus, calcium, and calcium-phosphorus product. Those outcomes are distinct from the primary target-attainment question.

The study includes a comparison with calcium carbonate in Part 2, but its non-randomized allocation and open-label design limit the interpretation of between-treatment differences. The stated primary endpoint is specifically for participants who received lanthanum carbonate in Part 2 or Part 3, and the result is not reported in the registry record. Therefore, the registry entry does not establish how often the target was reached or whether target attainment differed between treatments.

3. Trial Design

This Phase 2 study is described as a three-part, open-label investigation of lanthanum carbonate in children and adolescents with chronic kidney disease on dialysis. The registry lists chronic kidney disease and hyperphosphatemia as the conditions of interest. Enrollment is recorded as 63. The study is marked completed; its recorded start date is 2013-02-15 and its primary completion date is 2018-11-16. Shire is listed as the sponsor.

The official study title describes pharmacokinetic assessment, an 8-week comparison of lanthanum carbonate and calcium carbonate using a crossover design, and an 8-month investigation of lanthanum carbonate. The registry identifies the model as crossover but also identifies allocation as non-randomized and masking as none. Thus, the design description includes treatment periods and a crossover structure, but it does not describe a randomized, blinded comparison. The details of sequence assignment and the timing or handling of any period effects are not reported in the registry record.

For lanthanum carbonate, the recorded regimen is an oral total daily dose of 1500 mg to 3000 mg, divided and mixed equally between three meals. For calcium carbonate, the oral daily dose was adjusted as appropriate until the target serum phosphorus level was achieved or a maximum daily dose of 6500 mg was reached. These dosing descriptions do not by themselves establish how doses were selected for individual participants or how dose changes were analyzed; those details are not reported in the registry record.

The primary endpoint combines participants receiving lanthanum carbonate in Part 2 and/or Part 3, and the endpoint description says the results were analyzed according to intervention received rather than by study part. It also restricts the described population to participants with the specified treatment and serum phosphate assessment information. The registry record does not provide the outcome value, a treatment-effect estimate, or an analysis output. The crossover structure may allow within-participant treatment observations, but the posted record does not provide enough analysis detail to determine how those observations contributed to a comparative estimate.

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: It was a 3 part study (Part 1: Pharmacokinetic assessment, Part 2: \[Part 2a-calcium carbonate and lanthanum carbonate {crossover comparison} or Part 2b-lanthanum carbonate\], Part 3: lanthanum carbonate treatment for 6 months). Overall 63 participants enrolled in the study.

Part 1: Single Dose Lanthanum Carbonate

Reasons for not completing this period:

Part 2a: Calcium Carbonate + Lanthanum

Reasons for not completing this period:

Part 2b: Lanthanum Carbonate (8 Weeks)

Reasons for not completing this period:

Part 3: Lanthanum Carbonate (6 Months)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-protocol set 2 (PP2) included participants who had taken at least 1 dose of investigational product and completed 8 weeks of treatment with lanthanum carbonate and who had serum phosphate assessment data available during Part 2 or Part 3 to allow summarizing the percentage of participants achieving age-specific KDOQI target.

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: Safety analysis set 1 and 2 included all participants who had taken 1 dose of IP in Part 1 for SAS 1, Part 2 or 3 for SAS 2 and who had completed at least 1 follow-up safety assessment. Few participants were analyzed in multiple arms/periods within the study, hence to avoid the duplication, baseline was analyzed only for the overall participants.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Achieving Age-Specific Kidney Disease Outcomes Quality Initiative (KDOQI) Targets for Serum Phosphate Level Following 8 Weeks of Lanthanum Carbonate Administration (Part 2 + Part 3), measured over After 8 weeks of lanthanum carbonate administration in Part 2 and/or in Part 3.

The primary endpoint is the percentage of participants achieving age-specific Kidney Disease Outcomes Quality Initiative (KDOQI) serum phosphorus targets after 8 weeks of lanthanum carbonate administration in Part 2 and/or Part 3. For adolescents aged 12 years to under 18 years, the target is at most 5.5 mg/dL (1.78 mmol/L). For children aged 10 years to under 12 years, the target is at most 6.0 mg/dL (1.94 mmol/L). These are separate thresholds, so the endpoint accounts for age rather than applying one cutoff to the whole study population.

As a general statistical concept, a percentage achieving a threshold summarizes the proportion classified as meeting a prespecified criterion. It can be easier to interpret as target attainment than a mean change, but it also discards information about how far measurements lie above or below the threshold. Participants close to either side of a cutoff are classified differently even when their measurements are similar. The percentage also depends on which participants have usable assessment data and are included in the analysis.

The registry describes the primary population as participants who had taken at least one dose of investigational product, completed 8 weeks of lanthanum carbonate treatment, and had serum phosphate assessment data available during Part 2 or Part 3. The population description is truncated in the record, so additional detail is not reported in the registry record. The actual percentage and its precision are not reported in the registry record. Without those results, the endpoint definition can be explained, but the frequency of target attainment cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary percentage: whether a participant met the age-specific serum phosphorus threshold after the specified lanthanum carbonate treatment. In general, a binary endpoint converts each participant's measurement into one of two categories. The percentage is calculated from the number classified as meeting the target relative to the relevant analysis population. The registry gives the endpoint definition and a description of the intended population, but it does not report the resulting count or percentage. No recalculated estimate is available from the posted results.

The endpoint population is described as per-protocol set 2. The record says this set included participants who had taken at least one dose of investigational product, completed 8 weeks of lanthanum carbonate treatment, and had serum phosphate assessment data available during Part 2 or Part 3. As a general concept, a per-protocol analysis focuses on participants who meet specified treatment and data requirements. Its result may differ from an analysis that includes all participants assigned or exposed to treatment, because exclusions can change the population being described. The record's population text is cut off, so the full eligibility details are not reported in the registry record.

The registry states that the primary endpoint was analyzed and presented according to the intervention received, not separately by study part. In general, analysis according to treatment received describes outcomes by exposure rather than preserving a randomized assignment. This distinction matters especially when allocation is non-randomized: characteristics that influence treatment received can also be associated with the outcome. An unadjusted difference between such groups may therefore reflect group composition as well as treatment. No adjustment method or comparative estimate is reported in the registry record.

The study is labeled crossover, and the official title describes an 8-week treatment comparison. General methods for crossover studies must consider that observations from the same participant can be related, and that period or sequence may influence outcomes. A simple analysis treating all observations as independent can misstate uncertainty when measurements within a participant are correlated. The record does not report the model used, the treatment sequence, or how within-participant correlation and possible period or carryover effects were handled. It is therefore not possible to assess whether a specific crossover analysis was applied.

For an outcome expressed as a percentage, uncertainty depends in part on the number of eligible observations and the balance between participants meeting and not meeting the target. A confidence interval can communicate uncertainty around the estimated percentage. General interval methods differ in their assumptions and performance, particularly when the sample is limited or the observed proportion is near an endpoint. The registry record does not report a confidence interval, standard error, or statistical method for the primary percentage. No uncertainty interval should be inferred from the endpoint description or overall enrollment.

The registry lists 18 outcome measures and zero analyses. These record-level counts do not specify a multiplicity adjustment or prove that no analysis was conducted outside the posted registry entry. When many outcomes or comparisons are examined, general statistical practice recognizes that the chance of at least one apparently unusual result can increase. Prespecified outcome hierarchies or multiplicity adjustments can address that issue, but the registry record does not report whether either approach was used. It also does not report interim analyses, and no interim-analysis plan should be assumed.

The study description includes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a fraction of the observed effect. This is a planning framework, not evidence that the trial was designed using those assumptions. A planning sample size is not observed power, and it cannot establish the precision of a result that is not posted. The registry record does not report the trial's own sample-size justification.

As a general matter, missing outcome data can affect a percentage if participants without measurements differ from those with measurements. A complete-case or available-assessment calculation describes only those with usable data unless further methods are used. The endpoint population explicitly requires serum phosphate assessment data, but the extent and handling of missing data are not reported in the registry record. The record also does not report sensitivity analyses for missing outcomes. Without these details and the outcome estimate, the robustness of the primary result cannot be evaluated.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Part 2 + Part 3: Lanthanum Carbonate")
n      <- c(34)
events <- c(17)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Part 2 + Part 3: Lanthanum Carbonate  34  17  50.0  32.4  67.6  34.1  65.9  34.0  66.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures, including the primary target-attainment outcome and secondary measures of serum phosphorus, calcium, and calcium-phosphorus product. Having multiple outcomes raises a general interpretive issue: if many hypotheses are tested, some may appear notable by chance. Statistical plans can address this through a prespecified hierarchy, adjustment, or careful emphasis on a limited primary question. Whether this study used any such approach is not reported in the registry record. The record lists zero analyses, so it does not provide analysis outputs from which a multiplicity strategy could be assessed.

Missing-data handling is also important because the primary endpoint population requires serum phosphate assessment information after treatment. In general, the percentage calculated among participants with available measurements may not represent all enrolled participants if availability is related to outcome or treatment experience. The registry record does not report how many primary endpoint observations were missing, reasons for missingness, or any imputation or sensitivity method. The population description is truncated, leaving additional eligibility details not reported in the registry record.

The endpoint uses a per-protocol population rather than describing an all-enrolled analysis. As a general concept, restricting analysis to participants who completed treatment and met assessment requirements can make the analyzed group differ from the original study population. How the resulting estimate should be generalized depends on the eligibility rules and the reasons participants were excluded or lacked measurements. Those details and the primary outcome result are not reported in the registry record.

Interim analyses and the statistical plan are not reported in the registry record. No multiplicity correction, missing-data assumption, or sample-size justification should be inferred from the study's outcome list or design labels.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: peritonitis (9.6%), device related infection (3.8%), hypertension (3.8%), osteochondrosis (1.9%), abdominal pain (1.9%).

The registry's serious adverse event figures list 0 of 20 participants for Part 1: Lanthanum Carbonate, 9 of 53 for Part 2: Calcium Carbonate, and 19 of 52 for Part 2 + Part 3: Lanthanum Carbonate. The corresponding number of participants with other adverse events is listed as 2 of 20, 10 of 53, and 20 of 52. Deaths are listed as 0 in each group. These are descriptive registry figures for the named groups and periods.

The record also lists serious adverse event terms and percentages: Peritonitis, 9.6%; Device related infection, 3.8%; Hypertension, 3.8%; Osteochondrosis, 1.9%; Abdominal pain, 1.9%; and Nausea, 1.9%. The registry record does not provide enough detail in these figures to establish how terms overlap within participants or to support a causal interpretation.

These groups do not constitute a like-for-like randomized comparison. The study is recorded as non-randomized and open-label, and the group descriptions cover different parts or treatment periods. The counts should not be compared as if they came from balanced concurrent randomized groups. A zero death count means no deaths are listed in these groups; it does not establish the absence of risk. The figures also do not describe severity beyond the serious-event classification or replace the complete safety reporting, which is not reported in the registry record.

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

The registry entry describes a study of lanthanum carbonate and calcium carbonate in children and adolescents with chronic kidney disease on dialysis, and it defines a primary target-attainment outcome. The target differs by age: at most 5.5 mg/dL (1.78 mmol/L) for adolescents aged 12 years to under 18 years, and at most 6.0 mg/dL (1.94 mmol/L) for children aged 10 years to under 12 years. This definition clarifies what counts as meeting the primary endpoint.

However, the primary outcome result is not reported in the registry record. There is no posted percentage of participants reaching the target, no comparative effect estimate, and no uncertainty interval for that endpoint. Therefore, the entry does not show how frequently target attainment occurred or how precisely it was estimated. It also does not support a conclusion about the relative efficacy of lanthanum carbonate and calcium carbonate.

The study's design labels and descriptions matter to interpretation. It is open-label and non-randomized, although the official title describes a crossover treatment comparison. General statistical reasoning cautions that treatment differences in a non-randomized study may reflect differences in participants, periods, or other factors as well as treatment. The registry record does not report the analysis methods needed to judge how those issues were handled.

The listed safety counts describe adverse events in the named groups, but their different study periods and non-randomized allocation limit direct comparisons. The figures do not establish that a treatment caused an event, nor does a zero count for a listed outcome establish that the outcome cannot occur.

In short, the registry record is informative about the study question, treatment descriptions, endpoint criteria, and selected safety counts. It is not sufficient to judge the primary endpoint result, its precision, or a causal treatment contrast. Those outcomes and their analysis are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable for combining a target-based primary endpoint with a crossover design and a non-randomized allocation. Each feature changes what an estimate would mean. The age-specific threshold makes the endpoint clinically structured, but a percentage meeting a threshold does not retain the full information in each participant's serum phosphorus measurement. The crossover label means repeated observations may be relevant, while non-randomized allocation means a simple comparison cannot automatically be interpreted as an unbiased treatment effect.

The endpoint's population definition also highlights that analysis results depend on who contributes data. Participants had to receive lanthanum carbonate, complete the specified treatment duration, and have an assessment available under the stated description. In general, such restrictions can affect how well the result represents the original study population. The full population description and missing-data methods are not reported in the registry record.

The registry includes several outcomes and multiple study parts, but lists zero analyses and does not report the primary endpoint result. This distinction is important: a detailed endpoint definition is not the same as a posted estimate, and a planned or listed outcome does not show what the observed data found. Without an effect estimate and uncertainty interval, readers cannot assess precision or compare the result with a meaningful benchmark.

The posted adverse-event figures are useful as descriptive reporting, but differences between the listed groups should not be treated as randomized safety effects. They cover different parts and treatment periods, and the allocation is recorded as non-randomized. The record's value is therefore chiefly in documenting the design and outcome definitions, while its missing analysis results constrain statistical conclusions.

15. 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.

A central limitation of the registry record is that it does not report the primary endpoint result, despite describing the endpoint and its age-specific thresholds. The primary population description is truncated, and the complete analysis population cannot be reconstructed from the posted text. No confidence interval, treatment-effect estimate, or p-value for the primary outcome is reported in the registry record.

The design is labeled crossover, but allocation is non-randomized and masking is absent. These features limit straightforward treatment comparisons. The registry does not report treatment sequence details, a statistical model, or methods for addressing period, sequence, or carryover effects. It also does not report whether any adjusted comparison was performed.

The primary endpoint population requires treatment completion and available serum phosphate assessment data. The number and reasons for missing assessments, the handling of missing outcomes, and sensitivity analyses are not reported in the registry record. The effects of this restriction on interpretation cannot be assessed without those details.

The record lists 18 outcome measures but no analyses. A multiplicity strategy, interim-analysis plan, and statistical analysis plan are not reported. The sample-size planning assumptions described in the record are not the trial's documented design justification, which is not reported in the registry record.

Safety counts are reported for groups covering different study parts or periods. Since the study is non-randomized, those counts do not establish a comparative treatment effect or a causal relationship. The registry's selected safety figures also do not provide a complete assessment of event context or participant-level overlap, which is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Assess the Pharmacokinetics of Lanthanum Carbonate, Investigate and Compare the Efficacy, Safety and Tolerability of Lanthanum Carbonate With Calcium Carbonate in Hyperphosphataemic Children and Adolescents With Chronic Kidney Disease on Dialysis — NCT01696279.
• Registry record last updated 2021-06-10; status last verified 2021-05.
• Results first posted 2020-01-02.
• 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.

19. Record Summary

This completed Phase 2 study enrolled 63 participants with hyperphosphatemia and chronic kidney disease on dialysis. The record describes a three-part, open-label study, a crossover model, non-randomized allocation, and lanthanum carbonate and calcium carbonate treatment. The primary endpoint is the percentage meeting age-specific KDOQI serum phosphorus targets after 8 weeks of lanthanum carbonate in Part 2 and/or Part 3.

The registry defines separate thresholds for participants aged 10 years to under 12 years and those aged 12 years to under 18 years. It does not report the primary endpoint percentage, a comparative effect estimate, or uncertainty around the result. It lists selected serious and other adverse event counts for the treatment groups, but those groups are not a randomized like-for-like comparison. Details of the statistical plan, missing-data handling, multiplicity, and crossover analysis are not reported in the registry record.