Pharmacodynamics, Efficacy and Safety of Basiliximab 40 or 80 mg in Combination With Ciclosporine Microemulsion or Everolimus, in Adult Low Risk de Novo Renal Transplant Recipients (IDEALE Study): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacodynamics, Efficacy and Safety of Basiliximab 40 or 80 mg in Combination With Ciclosporine Microemulsion or Everolimus, in Adult Low Risk de Novo Renal Transplant Recipients (IDEALE Study) (NCT01596062), a randomized phase 2 study. The primary outcome is Area Under the Curve (AUC) of CD25 Saturation by Basiliximab From Day 0 to Day 84.

2. Clinical Question

3. Trial Design

The registry describes a randomized, open-label, parallel-group Phase 2 study of basiliximab regimens in low-risk adults receiving a new kidney transplant. The study is titled IDEALE and lists renal transplantation as its condition. The sponsor is Novartis Pharmaceuticals. Enrollment was 16, and the registry status is completed. The recorded start was 2012-03 and primary completion was 2013-03.

The three treatment groups received cumulative basiliximab doses of 40 mg or 80 mg. In the 40 mg group, the regimen included Neoral®, Myfortic® and corticosteroids, with basiliximab 20 mg at D0 and 20 mg at D4. One 80 mg group received Neoral®, Myfortic® and corticosteroids, with basiliximab 40 mg at D0 and 40 mg at D4. The other 80 mg group received Certican®, Myfortic® and corticosteroids, with the same basiliximab dosing schedule. The registry describes that latter regimen as calcineurin inhibitor-free.

There was no masking. The official title describes a 12-week study with an additional 12 weeks of follow-up. The primary endpoint was assessed at Day 84, Week 12 after transplantation. Listed secondary outcomes include pharmacodynamic measures, cell populations, biopsy-proven acute rejection, treatment failures and estimated glomerular filtration rate at Day 8 and Week 24. Details of the randomization procedure, allocation concealment, site count and protocol deviations are not reported in the registry record.

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: PK/PD population: Patients included in the ITT population for whom at least one blood sample for PK/PD analyses was collected. This population is the reference population for the PK and PD analyses.

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.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Curve (AUC) of CD25 Saturation by Basiliximab From Day 0 to Day 84, measured over Day 84 (Week 12) after transplantation.

The primary endpoint is the mean area under the curve (AUC) of CD25 saturation by basiliximab from Day 0 to Day 84, corresponding to Week 12 after transplantation. The unit is weeks multiplied by the percentage of saturated CD25. The registry defines CD25 saturation as the percentage of T cells expressing CD25. The AUC combines measurements over the stated period into a measure of the accumulated saturation pattern, rather than representing a single measurement at Day 84.

A pharmacodynamic endpoint can describe how a drug relates to a biological target or response. In this study, CD25 saturation was selected to examine receptor binding over time under different basiliximab regimens. The study aims specifically included examining receptor saturation and expression across two doses and comparing saturation measurements with and without Neoral®.

The endpoint is reported as a mean with standard deviation. The registry says the mean AUC was calculated only for patients who received two Simulect® injections. Its defined PK/PD population includes patients in the ITT population for whom at least one blood sample for PK/PD analyses was collected; that population is identified as the reference population for PK and PD analyses. The number contributing to each posted arm result is reported alongside the mean. No confidence intervals or comparative test results are reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous primary outcome summarized as a mean and standard deviation. The analysis description identifies the PK/PD population and says that the mean AUC was calculated only for patients who received two Simulect® injections. It does not report the statistical model used for comparisons, adjustment variables, handling of repeated measurements, or any hypothesis tests. No comparative analyses are posted in the registry record.

What does a mean and standard deviation describe?

In general, a mean is an average across the observations included in a group summary. A standard deviation describes how dispersed those observations are around the mean. It is not the same as a confidence interval: the standard deviation describes variation among observations, whereas a confidence interval expresses uncertainty about an estimated quantity under a statistical method. No confidence intervals are reported for these primary results.

The AUC endpoint integrates CD25 saturation measurements over the Day 0 to Day 84 interval. In general, an AUC can retain information about a response across time that would be lost by looking at one measurement alone. The registry does not describe the sampling schedule, the method for calculating the AUC, or how missing measurements within the interval were handled. Those particulars are not reported in the registry record.

How should the group sizes be read?

The primary group results give n=3, n=6 and n=6. These are the numbers associated with the reported arm-level endpoint summaries, rather than the overall enrollment figure. The endpoint description adds that mean AUC was calculated only for patients who received two injections, while the PK/PD population definition requires at least one blood sample and membership in the ITT population. The registry does not explain how these criteria led to the number contributing to each mean, nor does it report the amount or pattern of missing endpoint data.

For a continuous endpoint, small group sizes limit how precisely a group mean can characterize the population value. The observed standard deviation offers information on variability in the analyzed observations but does not, on its own, provide a direct estimate of the uncertainty in a difference between groups. A comparative standard error or confidence interval would require an analysis and assumptions not reported in the registry record.

What do the planning illustrations represent?

General power calculations address the chance that a planned analysis will detect an effect under specified assumptions. The planning illustrations described for this study use the observed effect, a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. They consider effects defined as stated fractions of the observed effect. They are planning illustrations, not observed power and not a report of the study's original design justification. The registry does not report the protocol's sample-size justification. The numeric planning outputs and the fractions used are not reported in the registry record.

In general, sample-size calculations depend on the assumed effect, variability, significance level, allocation and analysis method. A calculation based on an effect observed in a small study can be unstable, because the observed effect may not represent the underlying effect reliably. It should not be read as proof that the trial had adequate power or as a result observed in participants.

Why does dispersion matter?

In general, variability affects the precision of a mean and of comparisons involving means. Over-dispersion means that observed variability is greater than a statistical model assumes. If such a model is used without accounting for extra variability, uncertainty estimates may be too narrow. The registry reports standard deviations for the primary endpoint but does not report a distributional assessment or a model that would allow evaluation of over-dispersion. No conclusion about a particular distribution or model fit is possible from the posted summaries alone.

The registry identifies a randomized parallel design, but does not state whether the analysis followed intention-to-treat for the primary endpoint, whether a particular contrast was prespecified, or whether estimates were adjusted for baseline or other covariates. These aspects of the statistical plan are not reported in the registry record. Consequently, the arm means and standard deviations are the available basis for interpreting the primary outcome.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Simulect 40mg + Neoral + Myfortic + Steroids", "Simulect 80mg + Neoral + Myfortic + Steroids", "Simulect 80mg + Certican + Myfortic + Steroids")
n   <- c(3, 6, 6)
m   <- c(8.4, 11.1, 9.7)
sp  <- c(1.61, 1.12, 0.7)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Simulect 40mg + Neoral + Myfortic + Steroids  3  8.400  1.610  4.401  12.399
CARM  Simulect 80mg + Neoral + Myfortic + Steroids  6  11.100  1.120  9.925  12.275
CARM  Simulect 80mg + Certican + Myfortic + Steroids  6  9.700  0.700  8.965  10.435

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures, including the primary endpoint and secondary outcomes involving pharmacodynamic measures, immune cell populations, biopsy-proven acute rejection, treatment failures and eGFR. Seven secondary outcomes are posted, but the registry does not report comparative analyses for them. The number of analyses is reported as zero. A multiplicity strategy for assessing multiple outcomes or multiple treatment comparisons is not reported in the registry record.

Multiplicity matters in general because examining several outcomes or comparisons can increase the chance of at least one apparently notable result arising by chance. Statistical plans may address this through prespecified primary comparisons or adjustment procedures, but no such procedure is reported in the registry record. It would therefore be inappropriate to infer how multiplicity was handled or to treat the listed secondary outcomes as confirmatory evidence.

The primary endpoint population is described as patients in the ITT population with at least one blood sample collected for PK/PD analyses. The registry also states that mean AUC was calculated only for patients who received two Simulect® injections. It does not report how many patients were excluded from the endpoint calculation, the reasons for missing measurements, or any method for imputing or otherwise handling missing data. The relationship between the defined PK/PD population and the requirement for two injections is not further explained.

Missing-data methods can affect interpretation when the availability of measurements is related to participant characteristics or outcomes. General approaches depend on assumptions about why observations are absent; no such assumptions or procedures are reported in the registry record. Thus, the posted group summaries describe the participants contributing to those summaries, and the extent to which they represent all randomized participants cannot be assessed from the registry information.

12. 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: transplant rejection (33.3%), femur fracture (33.3%), graft loss (33.3%), post procedural haematuria (33.3%), renal failure acute (28.6%).

The registry reports serious-event and other-event counts by treatment group, with the number at risk stated for each category. In the 40 mg basiliximab plus Neoral® group, 2 of 3 at risk were affected by serious events and 3 of 3 by other events. In the 80 mg basiliximab plus Neoral® group, 2 of 6 were affected by serious events and 6 of 6 by other events. In the 80 mg basiliximab plus Certican® group, 5 of 7 were affected by serious events and 6 of 7 by other events.

The serious-event terms listed include Transplant rejection, Femur fracture, Graft loss and Post procedural haematuria, each reported as 33.3%; Renal failure acute at 28.6%; and Gastritis at 16.7%. The registry does not provide enough detail in these figures to determine the event-level denominators or whether participants could contribute to more than one listed term. These percentages should not be combined or interpreted as mutually exclusive categories.

Deaths are not reported in the registry record. The safety counts describe what was recorded in this small study; they do not establish comparative safety between regimens. Differences in group sizes and the absence of a reported comparative safety analysis limit interpretation.

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

The primary endpoint summaries describe mean CD25 saturation AUC values in three basiliximab regimen groups over the period from Day 0 to Day 84. The means and standard deviations show the central values and observed spread among those contributing to each group summary. They do not, by themselves, quantify a causal treatment effect or establish how precisely groups differ.

The study was randomized, but the registry record does not include comparative estimates, confidence intervals or hypothesis-test results for the primary endpoint. Random allocation is a design feature; it does not substitute for reporting the analysis results needed to estimate uncertainty around between-group differences. With no comparative analyses posted, the data do not support a statistical conclusion about whether one regimen produces a different AUC from another.

The group comparisons also involve distinct regimens. The 40 mg and 80 mg groups receiving Neoral® differ in basiliximab cumulative dose, while the two 80 mg groups differ in the accompanying immunosuppressive regimen. The registry's study aims include comparing CD25 saturation with and without Neoral®, but the reported arm summaries alone do not isolate that drug's contribution from other treatment differences.

The results are specific to the endpoint and analysis population described in the registry. They do not by themselves establish clinical efficacy, transplant outcomes, or safety differences. Although the registry lists biopsy-proven acute rejection, treatment failure and eGFR among secondary outcomes, comparative results for these outcomes are not reported in the registry record. Nor are details of missing-data handling or the full analysis plan reported.

In general, estimates from small groups have substantial potential uncertainty, and an arm mean should not be treated as a precise estimate of the value expected in a broader population. The posted standard deviations provide information about variability within the analyzed groups, but without confidence intervals or a specified comparative model, the precision of treatment contrasts remains unquantified. The findings are therefore best understood as descriptive pharmacodynamic results from this completed Phase 2 study.

14. Why This Trial Matters Statistically

This trial is statistically notable for its focus on a pharmacodynamic endpoint rather than a clinical event as the primary outcome. The AUC of CD25 saturation summarizes receptor-related measurements over time, reflecting the study's stated interest in basiliximab dose and receptor saturation. Such endpoints can provide a biological description of treatment regimens, but their interpretation depends on clear measurement and analysis details.

The three-arm design brings together two questions: variation in cumulative basiliximab dose alongside Neoral®, and comparison of two 80 mg basiliximab regimens with different accompanying therapy. Those questions are related but not identical. Separating the effect of one treatment component from another requires contrasts that align with the design and a clearly reported analysis. The registry lists the intended regimen groups but does not report comparative estimates.

The difference between overall enrollment and the arm counts for the primary endpoint makes transparent reporting of analysis populations especially relevant. The registry defines the PK/PD population and adds a two-injection condition for the AUC mean, yet does not describe the participant flow into each endpoint summary. Clear accounting of randomized, treated, measured and analyzed participants helps readers understand what population each statistic represents.

The record also illustrates why descriptive values should be accompanied by uncertainty and analysis details. Means and standard deviations are useful summaries, but they cannot replace confidence intervals, prespecified comparisons or documentation of missing-data and multiplicity procedures. The registry's zero posted analyses leaves the primary results descriptive, making restraint in comparative interpretation essential.

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.

The primary endpoint groups are small, with reported n values of 3, 6 and 6. This limits how fully the group summaries can characterize variability and makes the means potentially sensitive to individual observations. The registry does not provide individual measurements, confidence intervals or comparative estimates that would show the uncertainty around the group results or differences between them.

The study is open-label, and no masking was used. The primary endpoint is a laboratory-based pharmacodynamic measure, but the registry does not report whether laboratory assessment or endpoint processing was blinded. Details of randomization generation, allocation concealment, site count and protocol deviations are also not reported in the registry record.

There is limited information about data completeness. The endpoint population definition refers to at least one blood sample, while the AUC mean is described as calculated only for patients who received two injections. The registry does not explain how many participants met each criterion, how measurements were handled when incomplete, or why the primary endpoint group counts differ from overall enrollment.

The treatment groups differ in more than one aspect across some comparisons. In particular, the 80 mg groups use different accompanying immunosuppressive regimens. Without posted comparative analyses and a specified contrast, differences in their descriptive results cannot be attributed to a single regimen component. The registry also does not report a multiplicity procedure, a statistical model, or the study's sample-size justification.

Finally, the listed secondary outcomes do not have posted comparative results in the registry record. The available primary summaries therefore do not establish effects on rejection, treatment failure, eGFR or other clinical outcomes, and the record does not report deaths.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacodynamics, Efficacy and Safety of Basiliximab 40 or 80 mg in Combination With Ciclosporine Microemulsion or Everolimus, in Adult Low Risk de Novo Renal Transplant Recipients (IDEALE Study) — NCT01596062.
• Registry record last updated 2014-07-25; status last verified 2014-06.
• Results first posted 2014-07-25.
• 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

IDEALE was a completed randomized, open-label, parallel-group Phase 2 study sponsored by Novartis Pharmaceuticals. It enrolled 16 low-risk adults receiving a new kidney transplant and compared three basiliximab regimens through a primary endpoint assessed at Day 84, Week 12 after transplantation.

The primary outcome was mean AUC of CD25 saturation by basiliximab. Posted group means were 8.4, 11.1 and 9.7, with standard deviations 1.61, 1.12 and 0.7, respectively; the corresponding group sizes were n=3, n=6 and n=6. The registry reports zero analyses, so comparative statistical results and confidence intervals are not reported in the registry record.

The record lists secondary pharmacodynamic and clinical outcomes, but comparative results for them are not reported. Details of missing-data handling, multiplicity procedures and the statistical analysis plan are not reported in the registry record.