Multicenter, Prospective, Rand, PK Study of LCP-Tacro™ Compared to Prograf® Capsules in De Novo Adult Kidney Transplant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multicenter, Prospective, Rand, PK Study of LCP-Tacro™ Compared to Prograf® Capsules in De Novo Adult Kidney Transplant (NCT01666951), a randomized phase 2 study. The primary outcome is Pharmacokinetics (AUC) of LCP-Tacro Compared to Prograf After Kidney Transplantation.

2. Clinical Question

3. Trial Design

The registry describes a Phase 2, prospective, randomized, multicenter, parallel-group study. Its official title characterizes the study as double-blind and double-dummy, while the registry's masking classification is quadruple. The record does not specify which people or roles were masked, so those descriptions cannot be reconciled further from the registry record.

The study compared LCP-Tacro tablets administered once daily with Prograf capsules administered twice daily. The purpose stated in the registry was to evaluate the pharmacokinetics of these regimens after kidney transplantation. The official title also describes the study in the context of prevention of acute allograft rejection, but the posted primary outcome is pharmacokinetic exposure, not an acute rejection outcome.

The study enrolled 36 participants. The primary PK assessment population consisted of 26 patients: 14 in the LCP-Tacro group and 12 in the Prograf group. Safety reporting uses a denominator of 17 in each group. The registry does not explain the differences among these reported populations or give a participant flow account that would clarify them.

The study started in 2012-11, had primary completion in 2013-03, and is listed as completed. The registry lists Renal Failure as the condition. It identifies Veloxis Pharmaceuticals as sponsor. No original sample-size justification, allocation ratio, or detailed operational description of the masking is reported in the registry record. These absences limit how fully the design can be reconstructed from the posted information.

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: The PK assessments were performed on the PK populations set which consists of 26 patients, 14 of whom received LCP-Tacro and 12 of whom who received Prograf.

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 two patients that were randomized but not does (one in eacj treatment arm) are not included in the demographics

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (AUC) of LCP-Tacro Compared to Prograf After Kidney Transplantation, measured over 1 days.

The primary endpoint was the pharmacokinetic parameter AUC, evaluated on Day 1 in adult de novo kidney recipients. AUC, or area under the concentration-time curve, summarizes drug exposure over a specified interval. In this study, samples were collected from 0 to 24 hours post dose, and the unit was ng*hr/mL. As a general pharmacokinetic concept, AUC is useful when a study aims to compare exposure over time rather than a single concentration measurement.

The registry reports the endpoint as a mean, with standard deviation as the measure of spread. The reported mean was 382.7 ng*hr/mL for LCP-Tacro and 147.8 ng*hr/mL for Prograf. The corresponding standard deviations were 233.8 and 85.31. These summaries describe the observed values in the PK assessment population; the standard deviations describe variability among observations, not the precision of the group means.

The endpoint addresses a drug-exposure question. It does not, by itself, establish whether transplant rejection occurred, whether clinical outcomes differed, or how the regimens compare on outcomes other than the recorded pharmacokinetic measure. Those results are not reported in the registry record.

7. Results Posted in the Registry

• Prograf: mean 147.82 versus 382.72 on control; difference -234.90 (95% CI -366.56 to -103.24), standardized effect d = -1.29; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: AUC is recorded on a numerical scale in ng*hr/mL. For a continuous outcome, a group mean gives a summary of the central value, while a standard deviation describes how dispersed participant observations are around that mean. These summaries answer different questions. A standard deviation is about variation among observations; a confidence interval for a mean difference is about uncertainty in the estimated group contrast.

What does the mean difference represent?

The posted comparison is labeled as Prograf relative to LCP-Tacro. The reported group means are 147.8 for Prograf and 382.7 for LCP-Tacro, and the reported mean difference is -234.9 ng*hr/mL. The negative direction is consistent with the lower Prograf group mean. The registry supplies the estimate and its confidence interval, but does not report the specific statistical test or model used to obtain them. It is therefore appropriate to describe the posted contrast without attributing it to a particular procedure.

How should the p-value be understood?

The registry reports an unadjusted p < 0.001. In general, a p-value measures how unusual data at least as incompatible with a null model as the observed data would be, if that model and the analysis assumptions held. It is not a measure of effect size, clinical importance, or the probability that a finding is due to chance. The unadjusted label means the reported value is presented without a multiplicity adjustment. Whether any other analysis considered multiple outcomes or comparisons is not reported in the registry record.

The p-value should be read with the estimated difference and confidence interval, not in isolation. The confidence interval communicates a range of values compatible with the data and the procedure used to construct it. The interval does not show the range of individual patient values; the standard deviations speak more directly to observed variation. The registry does not state the confidence-interval construction method or all assumptions used for the primary comparison.

Why does variability matter?

The standard deviation was 233.8 in the LCP-Tacro group and 85.31 in the Prograf group. In general, greater dispersion can make a group mean less precise when the sample size is fixed, because participant observations provide less concentrated information about the underlying mean. Variability also matters when considering whether a mean adequately represents a group: a mean can conceal asymmetry, unusual values, or subgroups. The registry does not report individual observations, distributional diagnostics, or a method for handling unusually influential observations.

The registry describes the endpoint as a mean and standard deviation. It does not report whether the analysis used a transformation, adjusted for covariates, or accounted for any center effects despite the multicenter design. Those details should not be inferred from the design label or from the numerical results.

What populations underlie the results?

The PK population contained 26 patients, with 14 in the LCP-Tacro group and 12 in the Prograf group. This analysis population is the relevant denominator context for the primary endpoint. Enrollment was 36, while safety reporting lists 17 participants at risk in each group. The registry does not provide enough participant-flow information to explain the distinctions among those populations. The reason for any exclusions from the PK assessment population and the handling of missing AUC measurements are not reported in the registry record.

In general, a complete-case analysis uses participants with the required measurements, while other approaches can incorporate incomplete observations under specified assumptions. The registry does not identify which approach was used or state whether missing primary outcome data occurred. It is therefore not possible to judge the effect of missingness from the posted summaries alone.

What does randomization contribute?

Random allocation is intended, in general, to reduce systematic differences between groups at the time of assignment. It does not guarantee identical groups, especially in a modest-sized study, and it does not eliminate uncertainty from sampling variability. The record identifies the study as randomized but does not report the allocation sequence method, concealment procedure, or allocation ratio. Those design details are not reported in the registry record.

The listed planning assumptions are for an illustrative sample-size exercise, not a description of the original trial analysis. They specify a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The analysis method used for the posted primary result remains unreported. Distinguishing the planning calculation from the trial's analysis prevents the planning assumptions from being mistaken for a documented protocol or test procedure.

Finally, the registry reports no analysis entries and no posted secondary outcomes. That does not establish that no analyses were conducted; it means additional analysis details and secondary results are not reported in the registry record. The posted primary result can be interpreted as a registry-reported comparison, while its full analytic context remains incomplete.

10. Confidence Intervals and Precision

The primary mean difference is -234.9 ng*hr/mL for Prograf relative to LCP-Tacro. Its confidence interval extends from -366.6 to -103.2 ng*hr/mL. A confidence interval is a general way to represent uncertainty around an estimate: under the method used, intervals constructed in the same way across repeated studies would capture the target value at the stated coverage rate. The registry does not report the confidence level or the construction method, so neither should be inferred beyond the interval as posted.

The interval lies on the negative side of zero, matching the direction of the reported group means. Its endpoints indicate that the estimated contrast is not pinpoint precise: a range of differences remains compatible with the reported analysis. The interval concerns the group mean contrast, not the distribution of individual AUC values. The group standard deviations, 233.8 for LCP-Tacro and 85.31 for Prograf, describe observed spread and are not substitutes for the interval.

Precision is also shaped by the size and composition of the analyzed population. The PK assessment included 14 LCP-Tacro patients and 12 Prograf patients. The overall enrollment was 36, but that larger count is not the analysis denominator for the primary endpoint. The registry does not explain why the PK population differs from enrollment or report missing-data handling, so the effect of those aspects on precision cannot be assessed from the record.

The unadjusted p < 0.001 is consistent with the posted interval and estimate, but a small p-value does not make an estimate exact. The confidence interval should be considered alongside the endpoint's limited timing and the reported sample sizes. Further details about the inferential method and interval assumptions are not reported in the registry record.

11. 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 planning figures are participants per arm, not total event counts. They are illustrative calculations based on the observed effect, rather than the trial's original sample-size justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial's own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the planned participants per arm under those assumptions for an 80% chance of detecting an effect of the specified size if that effect is present and the planning model applies. The 90% power column gives the corresponding participants per arm for a 90% chance under the same general interpretation. These are design quantities, not descriptions of what happened in the completed study. This is not observed power.

The rows use planning for 100% of the observed effect, planning for 75% of the observed effect, and planning for 50% of the observed effect. For 100%, the figures are 10 participants per arm for 80% power and 13 for 90% power. For 75%, they are 17 and 23; for 50%, they are 38 and 51. The figures increase as the assumed effect gets smaller: smaller effects are harder to distinguish from sampling variation and generally require more participants under the stated planning approach.

These calculations do not establish that the original study was designed around the observed effect, and they do not replace the registry's actual enrollment or PK analysis population. They are planning illustrations that depend on the stated assumptions. The registry does not report the original trial's sample-size rationale.

12. 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 = -234.900; pooled standard deviation σ = 181.534.
2. n = 2 × (1.96 + 0.842)² × 181.534² / -234.900² = 9.4, rounded up to 10 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 <- -234.9                      # observed difference in means
sigma <- 181.534047529658                     # 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(1666951)
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 = 10 (80% power), 13 (90% power)
 75% of observed effect: n per arm = 17 (80% power), 23 (90% power)
 50% of observed effect: n per arm = 38 (80% power), 51 (90% power)
power.t.test: 10.4 
Simulated power at n = 10 per arm: 0.783 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry reports one primary outcome and no posted secondary outcomes. It also lists zero analysis entries. These details describe what is available in the registry record; they do not establish that no additional analyses were conducted. The reported p-value is explicitly unadjusted. A multiplicity adjustment, if any, is not reported in the registry record.

Multiplicity matters in general when multiple outcomes, time points, subgroups, or comparisons are tested, because the chance of at least one small p-value can increase as testing expands. The record does not provide a full statistical analysis plan or a complete inventory of analyses, so the scope of any multiplicity issue cannot be determined. The primary result should therefore be understood as the posted unadjusted comparison, without assuming an adjustment or a prespecified testing hierarchy.

The registry identifies the PK assessment population as 26 patients: 14 who received LCP-Tacro and 12 who received Prograf. The record does not report the exact analysis-population rules, exclusions, or whether all intended Day 1 measurements were available. Missing-data methods and the extent of missing primary endpoint data are not reported in the registry record. The relationship between the overall enrollment of 36 and the PK assessment population is also not explained.

Safety results use 17 participants at risk per group, a different denominator context from the PK population. The record does not explain how participants were included in each analysis population. It also does not report whether analyses were adjusted for baseline characteristics, study center, or other variables. These absences restrict assessment of robustness and reproducibility; they do not support a conclusion about what procedures were or were not used outside the registry report.

14. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: kidney transplant rejection (11.8%), angina pectoris (5.9%), atrial fibrilation (5.9%), ventricular tachycardia (5.9%), nausea (5.9%).

The safety record lists 17 participants at risk in each group. It reports 5 participants affected by serious adverse events in the LCP-Tacro group and 5 in the Prograf group. These are descriptive registry counts. The record does not provide a statistical comparison between groups, and the reported counts do not establish whether an event was caused by a study drug.

The registry lists Kidney transplant rejection at 11.8% among the top serious adverse-event terms, and Angina Pectoris, Atrial Fibrilation, Ventricular Tachycardia, Nausea, and Vomiting at 5.9% each. The record does not specify arm-level attribution for these listed term frequencies, so they should not be assigned to either group from this information alone. The listing also does not establish event severity beyond its placement among serious adverse-event terms or provide timing and duration details.

Death counts are not reported in the registry record. Other adverse events are listed as affecting 17 participants in each group, but further detail about those events is not included in the information available for this summary. The safety figures should be read as registry-reported descriptions, not as evidence that the groups are equivalent or different in safety.

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

The result addresses a narrow statistical question: how the Day 1 mean AUC differed between the LCP-Tacro and Prograf groups in the PK assessment population. The reported means were 382.7 and 147.8 ng*hr/mL, respectively. The reported Prograf-relative-to-LCP-Tacro difference was -234.9, with a confidence interval from -366.6 to -103.2 and an unadjusted p < 0.001. These values describe the posted pharmacokinetic comparison.

They do not establish whether either regimen changes the risk of acute allograft rejection, improves transplant outcomes, or is preferable for an individual. Although prevention of acute allograft rejection is referenced in the official title, the primary posted endpoint is AUC. A primary rejection result and secondary outcome results are not reported in the registry record.

The result also does not show the full range of individual exposure values or what factors may explain the observed variation. Group standard deviations were 233.8 for LCP-Tacro and 85.31 for Prograf, but participant-level observations and distributional details are not reported. A difference in group means is not a description of every participant's response.

Interpretation is limited to Day 1 and the sampling interval from 0 to 24 hours post dose. The record does not report later pharmacokinetic measurements, repeated exposure comparisons, or the clinical consequences of the measured AUC values. The PK population comprised 26 patients, and the reason it differs from overall enrollment of 36 is not explained. These limits matter when judging how broadly the posted estimate can be applied.

The registry comparison is statistically distinct from a claim of clinical effectiveness or safety. The confidence interval conveys uncertainty around the group contrast, while the p-value describes compatibility with a null model under an analysis whose details are not reported. Neither statistic alone resolves the missing clinical and analytic context.

16. Why This Trial Matters Statistically

This study is statistically instructive because its primary question concerns pharmacokinetic exposure rather than a clinical event, even though acute allograft rejection appears in its official title. AUC captures exposure across a specified time interval, and the Day 1 sampling window is explicit: 0 to 24 hours post dose. That clarity helps define exactly what the reported means represent, while also making clear what they do not cover.

The comparison illustrates why estimates, uncertainty, and variability should be read together. The posted mean difference is -234.9 ng*hr/mL, and its confidence interval extends from -366.6 to -103.2. The group means and standard deviations provide complementary descriptions: the means summarize central values, and the standard deviations show spread. The p-value is unadjusted and is not a measure of clinical importance.

It also highlights the importance of identifying analysis populations. Overall enrollment was 36, the PK population was 26, and safety reporting used 17 participants at risk in each group. Those counts answer different denominator questions, and the registry does not explain how the populations relate. Without that context, readers should avoid treating one count as interchangeable with another.

Finally, the record leaves important analytic details unresolved. It does not report the original sample-size rationale, a complete analysis plan, missing-data methods, or an adjustment strategy for multiple analyses. The planning illustrations are therefore useful as conditional design calculations, not as proof about the original design or the completed study's power. The example demonstrates how registry results can support a focused statistical reading while still leaving uncertainty about methods and broader interpretation.

17. 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 is a Day 1 pharmacokinetic measure, based on samples collected from 0 to 24 hours post dose. It does not describe later exposure or a clinical outcome. The record does not report a primary comparison for acute allograft rejection, despite that topic's appearance in the official title.

The PK assessment population included 26 patients, with 14 in the LCP-Tacro group and 12 in the Prograf group. Overall enrollment was 36, and the safety record lists 17 participants at risk in each group. The registry does not explain the participant flow or the relation among these counts. Missing primary endpoint data, exclusions, and the rules defining the PK population are not reported.

The registry reports group means, standard deviations, a mean difference, a confidence interval, and an unadjusted p-value. It does not identify the inferential test, interval-construction method, use of covariate adjustment, or handling of study center. The original sample-size justification and detailed statistical analysis plan are also not reported in the registry record.

The study is labeled randomized and quadruple-masked, while its official title describes a double-blind, double-dummy design. The record does not explain the masking roles or provide details about randomization procedures. No secondary outcomes are posted, and there are no analysis entries. The record therefore offers limited information for evaluating the full analysis history or the completeness of outcome reporting.

Safety information is also limited: deaths are not reported in the registry record, and the listed serious adverse-event terms are not attributed to individual arms in the available summary. These constraints support a descriptive reading of the posted data rather than a broad conclusion about clinical outcomes or comparative safety.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Multicenter, Prospective, Rand, PK Study of LCP-Tacro™ Compared to Prograf® Capsules in De Novo Adult Kidney Transplant — NCT01666951.
• Registry record last updated 2015-07-07; status last verified 2015-06.
• Results first posted 2015-07-07.
• 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.

21. Record Summary

NCT01666951 is a completed, randomized, parallel-group Phase 2 study sponsored by Veloxis Pharmaceuticals. The registry lists enrollment of 36 and describes a prospective, multicenter comparison of once-daily LCP-Tacro tablets with twice-daily Prograf capsules in de novo adult kidney transplant recipients.

The primary outcome was Day 1 AUC over 0 to 24 hours post dose. The PK assessment population comprised 26 patients. The reported mean AUC was 382.7 ng*hr/mL for LCP-Tacro and 147.8 ng*hr/mL for Prograf; the Prograf-relative-to-LCP-Tacro mean difference was -234.9, with a confidence interval from -366.6 to -103.2 and an unadjusted p < 0.001.

The registry does not report secondary outcome results, a full analysis plan, or the original sample-size justification. Safety denominators and the PK population are different, and their relationship is not explained in the record.