Mycophenolate Mofetil 250 mg Capsules Under Fasting Conditions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mycophenolate Mofetil 250 mg Capsules Under Fasting Conditions (NCT00911274), a randomized phase 1 study. The primary outcome is Cmax - Maximum Observed Concentration.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, single-dose, 2-period, 2-treatment, 2-way crossover study of mycophenolate mofetil 250 mg capsules under fasting conditions. It was sponsored by Teva Pharmaceuticals USA and is recorded as completed. The registry lists healthy subjects and an enrollment of 53.

In a crossover design, each participant receives the treatments in sequence, rather than remaining in only one treatment group. The registry describes one sequence as receiving the test capsule first and CellCept® in the second period, and the other sequence as receiving CellCept® first and the test capsule second. Random allocation is recorded. Masking is listed as none, so the record does not describe blinding.

The treatment-level summaries report 53 observations for the test and 53 for the reference. These are not separate parallel groups: the design description indicates that treatment order varied across periods. The registry record does not state the length of any interval between periods, the washout procedure, or how period and sequence effects were addressed in the statistical analysis. Those details should not be inferred from the crossover label alone.

The primary endpoint was Cmax, with blood samples collected over a 72 hour period. The record identifies the primary population as all subjects who completed the study. It does not give the number completing the study, describe withdrawals, or explain how incomplete observations were handled. The posted record contains a sponsor-reported geometric test-to-reference analysis as well as treatment-level mean and standard deviation summaries.

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.

Period 1

Period 2

Analysis population for the primary outcome, as defined in the registry: Data from all subjects who completed the study was included in the statistical analysis.

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 Cmax - Maximum Observed Concentration, measured over Blood samples collected over 72 hour period.

Cmax means the maximum observed concentration of the measured substance after dosing. In this study it is reported in µg/mL, with blood samples collected over a 72 hour period. The registry identifies Cmax as the primary endpoint and states that bioequivalence was based on it.

As a general statistical concept, a maximum concentration is one way to characterize the peak of an exposure profile. It can capture whether one formulation produces a higher or lower observed peak than another, while not describing the entire concentration-time profile by itself. The timing of the peak and concentrations at other times are different features of exposure; the primary endpoint named in the record is specifically the maximum observed concentration.

The posted treatment summaries give a mean and standard deviation for each formulation. The test mean is 8.586 µg/mL and its standard deviation is 4.158; the reference mean is 9.217 µg/mL and its standard deviation is 3.889. The sponsor analysis instead reports a geometric test-to-reference ratio. These summaries use different scales and summarize the data in different ways, so they should not be treated as interchangeable.

In general, Cmax is useful for comparing peak concentrations, but interpreting it as evidence of bioequivalence requires a specified analysis and decision limits. The limits used by the sponsor are not reported in the registry record. Cmax alone also does not provide a complete account of all exposure characteristics or clinical outcomes.

7. Results Posted in the Registry

• Mycophenolate Mofetil (Test): mean 8.59 versus 9.22 on control; difference -0.63 (95% CI -2.16 to 0.90), standardized effect d = -0.16; z-test p = 0.420.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the treatment mean describe?

The registry reports a mean for each treatment. As a general statistical concept, a mean is a measure of the center of a set of observations: it adds the observed values and divides by the number of observations. The posted mean Cmax is 8.586 µg/mL for the test and 9.217 µg/mL for the reference. The mean describes the observed values on the arithmetic scale; it does not describe every participant's result or the spread around the center.

The standard deviation describes how dispersed observations are around their mean. The reported standard deviations are 4.158 for the test and 3.889 for the reference. In general, a larger standard deviation indicates greater variability in the observations around the mean. These summaries do not reveal the shape of the distributions or how each participant's test result relates to that participant's reference result. Individual paired data and the within-person correlation are not reported in the registry record.

What is the unadjusted recalculation?

The mean-difference comparison is an unadjusted recalculation from the posted treatment summaries. In general, a mean difference puts the contrast between two arithmetic means on the same measurement scale as the endpoint. Here the comparison is test relative to reference, so a negative estimate means the test mean is lower in the recalculation. The unadjusted p-value is 0.42, and the recalculated confidence interval includes zero.

This is not the same as a fitted crossover analysis. A crossover analysis can use the pairing of treatment observations within participants and may account for period or sequence terms. The registry record does not report the model used for the sponsor's analysis, and the recalculation does not recover participant-level information or adjust for design features. It should therefore be interpreted as a simple, unadjusted comparison based on the posted summaries.

What does the sponsor's geometric ratio represent?

The sponsor reports a geometric test-to-reference ratio multiplied by 100. In general, geometric summaries are based on multiplicative rather than additive comparisons and are commonly used when treatment comparisons are expressed as ratios. A value of 100 represents equal geometric levels for test and reference on this scale. The reported estimate is 92.41, with a 90% confidence interval from 82.77 to 103.18.

The geometric ratio is not the arithmetic mean difference. It uses a different scale and a different summary of the treatment data. The registry does not report the transformation, model, or other details used to produce the sponsor estimate. It also does not report a sponsor p-value for this analysis. Interpretation should stay with the reported ratio and interval rather than attempting to reconstruct the analysis from the arithmetic means.

How should a confidence interval be understood?

As a general statistical concept, a confidence interval gives a range of values compatible with the data and the method used, while reflecting sampling uncertainty. It is not a range that contains a fixed proportion of individual participants' results, nor does it by itself prove equivalence. The sponsor's interval is reported at 90% confidence. The confidence level for the unadjusted recalculation is not stated in the registry record.

For a ratio, the value 100 is the equal-ratio reference point; for a mean difference, zero is the no-difference reference point. The sponsor interval includes values below and above 100. The recalculated interval includes zero. Whether either interval supports a formal decision depends on the analysis and, for bioequivalence, the decision limits. Those limits are not reported in the registry record.

Why does crossover structure matter?

In general, a crossover design can compare treatments within the same participant, which can help account for stable differences between people. But the benefit of that pairing depends on a suitable analysis, and observations within a participant are not independent. If an analysis treats paired values as though they came from unrelated participants, its uncertainty estimate may not reflect the design. The registry's treatment summaries list the same observation count for each treatment, but do not include paired differences or their variability.

The record describes randomized treatment order and two periods, but does not report the washout interval, period effects, sequence effects, or the sponsor's modeling choices. Those omissions limit an independent assessment of whether the posted summary analysis reflects the crossover structure. They do not justify assuming that the sponsor did or did not account for these features.

What is not specified?

The registry records three outcome measures and three analyses, but only the primary endpoint is described in the registry entries, and no secondary results are posted. The statistical method field for the sponsor analysis is not specified. Multiplicity procedures, missing-data rules, handling of incomplete periods, and a detailed analysis population are not reported in the registry record. General statistical principles can explain why these details matter, but they cannot fill in the study's actual methods.

Multiplicity refers, in general, to the increased chance of a false-positive finding when many hypotheses are tested. Whether an adjustment is appropriate depends on the planned questions and analysis strategy; the record does not say whether one was planned or used. Missing-data procedures matter because incomplete observations can affect both estimates and uncertainty. The record states that all subjects who completed the study were included in the primary analysis, but it does not give completion counts or describe how missing observations were handled.

10. Confidence Intervals and Precision

The sponsor-reported geometric test-to-reference ratio is 92.41, with a 90% confidence interval from 82.77 to 103.18. The interval gives a sense of the uncertainty around the estimated ratio under the sponsor's analysis. It includes values below and above 100, the equal-ratio point on the percentage scale. The registry record does not state the acceptance limits used to judge bioequivalence, so the interval alone cannot determine whether a formal criterion was met.

The unadjusted recalculation has a confidence interval that includes zero, the reference point for a mean difference. Its unadjusted p-value is 0.42. The confidence level for that recalculated interval is not reported in the registry record. Because the recalculation uses arithmetic summaries and does not report the within-participant pairing, it may not represent the sponsor's crossover analysis.

In general, interval width reflects both variability and the amount of information available, together with the method used to estimate uncertainty. A confidence interval is not a guarantee that the true value lies within its endpoints, and it does not indicate how individual responses are distributed. The registry's summary standard deviations describe treatment-level dispersion, but the paired variation needed to independently assess precision for a crossover contrast is not reported.

The sponsor's interval is therefore the relevant posted precision estimate for the geometric ratio, while its model details and decision limits remain unavailable. The available results permit a description of the range of ratios compatible with that reported analysis, but not a definitive assessment against unreported acceptance limits.

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 sample-size figures are planning illustrations expressed as participants per arm, not total events. They use the observed effect as a starting point and show planning for 100% of that effect, 75% of the observed effect, and 50% of the observed effect. For 100% of the observed effect, the illustration gives 639 participants per arm for 80% power and 855 participants per arm for 90% power. For 75% of the observed effect, it gives 1,136 participants per arm for 80% power and 1,520 participants per arm for 90% power. For 50% of the observed effect, it gives 2,555 participants per arm for 80% power and 3,420 participants per arm for 90% power.

The stated planning assumptions 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. These are not the original design assumptions for this trial; those assumptions are not reported in the registry record. The figures are not observed power.

In plain terms, the 80% power column gives the illustrative participants per arm under the stated assumptions for a design with an 80% chance of detecting the specified effect if that effect is real. The 90% power column gives the corresponding illustration for a 90% chance. Smaller effects are harder to distinguish from random variation, so planning to detect smaller effects requires more participants under these assumptions. These values are not a retrospective measure of the study's success, and they do not replace a design calculation tailored to the study's crossover structure.

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 = -0.631; pooled standard deviation σ = 4.026.
2. n = 2 × (1.96 + 0.842)² × 4.026² / -0.631² = 638.6, rounded up to 639 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 <- -0.6312                      # observed difference in means
sigma <- 4.02588568454197                     # 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(911274)
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 = 639 (80% power), 855 (90% power)
 75% of observed effect: n per arm = 1,136 (80% power), 1,520 (90% power)
 50% of observed effect: n per arm = 2,555 (80% power), 3,420 (90% power)
power.t.test: 639.6 
Simulated power at n = 639 per arm: 0.801 (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. Analyses Reported by the Sponsor

The sponsor's posted result is a geometric test-to-reference ratio of 92.41, with a 90% confidence interval from 82.77 to 103.18. The registry describes this analysis as a bioequivalence-related analysis, but does not report the detailed statistical method or the acceptance limits used. The interval includes values below and above 100, so it should be read as an estimate with uncertainty rather than as a standalone declaration that a bioequivalence criterion was met.

The simple recalculation uses the posted arithmetic means and gives a negative unadjusted mean difference, with a confidence interval that includes zero and an unadjusted p-value of 0.42. It is not the same analysis as the sponsor's geometric ratio. In particular, the registry record does not provide enough detail to reproduce the sponsor's crossover model from the treatment summaries.

The record does not flag a discrepancy between the sponsor analysis and the recalculation. The sponsor's own analysis remains the primary reported result for the registered bioequivalence question; the recalculation is a complementary, unadjusted comparison, not a substitute for the sponsor's method. Missing model details and decision limits prevent an independent reconstruction or formal pass/fail assessment.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures and three analyses. It identifies Cmax as the primary endpoint, while no secondary results are posted. The names and results of the other measures are not reported in the registry record. The record also does not describe a multiplicity strategy or say whether any adjustment for multiple comparisons was planned or used.

As a general statistical concept, testing several outcomes or treatment contrasts can increase the chance of at least one apparently unusual result arising by chance. A multiplicity plan clarifies which questions are confirmatory and how uncertainty or decision thresholds should be interpreted across those questions. Without a reported plan, the posted primary result can be described, but the relationship between it and any other planned analyses cannot be assessed.

The primary population is described as all subjects who completed the study. The record does not report how many completed, how many had usable observations, or how missing or incomplete measurements were handled. It does not state whether the analysis required completion of both treatment periods, or how any partial crossover data were treated. The sponsor analysis population and its inclusion rules are not reported in the registry record beyond the general statement about completers for the primary endpoint.

In general, missing-data handling matters because the analyzed observations may differ from the participants originally enrolled, and the reasons for missingness can affect interpretation. The record does not give withdrawal reasons, imputation procedures, or sensitivity analyses. It also does not report whether analyses were specified in advance or how the crossover design's period and sequence features were incorporated. These gaps limit assessment of the analysis population and the robustness of the posted estimate; they do not establish that any particular problem occurred.

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

The posted results describe peak concentration summaries for a test mycophenolate mofetil capsule and CellCept® in a randomized crossover study of healthy subjects under fasting conditions. The arithmetic means are 8.586 µg/mL for the test and 9.217 µg/mL for the reference. The sponsor reports a geometric test-to-reference ratio of 92.41, with a 90% confidence interval from 82.77 to 103.18.

The sponsor interval includes the equal-ratio point of 100 and spans values on either side of it. The unadjusted recalculation's interval includes zero, and its p-value is 0.42. These descriptions convey uncertainty in the posted comparisons; they do not prove that the formulations are equivalent. A formal bioequivalence interpretation requires the prespecified analysis and acceptance limits, which are not reported in the registry record.

Nor does the result show that the treatments have identical concentration profiles. Cmax summarizes the maximum observed concentration and does not represent every measurement over the sampling period. The record does not provide the other outcome results, detailed participant-level data, or the analysis model needed to assess the full concentration-time profile and within-participant variation.

The study concerns a single dose in healthy subjects after fasting, so its findings should be understood within that study setting. The registry record does not report clinical outcomes, longer-term treatment, or outcomes in people with a health condition. The pharmacokinetic comparison does not, by itself, establish a clinical benefit or harm. It is best read as a report of the measured endpoint, the sponsor's ratio estimate and interval, and the limits of the available statistical detail.

16. Why This Trial Matters Statistically

This trial is statistically notable for its crossover structure. Each participant received both treatments in different periods, with randomized order. In general, crossover designs can reduce the influence of stable differences between participants because the treatment comparison can be made within the same person. That advantage depends on an analysis that respects the paired observations and the design's period structure.

The posted treatment summaries report means and standard deviations for each treatment, but do not report the distribution of within-participant differences or the model used for the sponsor analysis. Those omissions make it difficult to independently assess how precisely the crossover comparison was estimated. A simple unadjusted recalculation from treatment summaries is useful as a descriptive check, but it is not a reconstruction of a crossover model.

The sponsor's geometric ratio and confidence interval also illustrate why scale matters. An arithmetic mean difference and a geometric ratio answer related but not identical statistical questions. They should be interpreted according to their own methods and decision criteria. Because the registry does not state the sponsor's acceptance limits or model details, the ratio cannot be translated into a formal bioequivalence conclusion from the posted information alone.

Finally, the sample-size illustrations make clear that the assumed target effect matters to planning: the illustration requires more participants per arm for smaller fractions of the observed effect. These calculations are not the original study design assumptions and are not observed power. Together, the crossover design, differing comparison scales, and incomplete reporting show why estimates should be interpreted alongside the analysis method and its assumptions.

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 registry record describes a study in healthy subjects after an overnight fast of at least 10 hours. The primary result therefore pertains to that study population and setting; the record does not establish how results would compare in other populations or conditions. The study used a single dose, and the endpoint was maximum observed concentration. This does not provide a complete account of outcomes beyond the recorded pharmacokinetic comparison.

Although the design is identified as a randomized crossover, the registry does not report the washout interval, the handling of period or sequence effects, or the sponsor's statistical model. Treatment-level means and standard deviations do not reveal the within-participant variation that would help assess the precision of a paired comparison. The unadjusted recalculation is consequently limited and should not be treated as the sponsor's full analysis.

The sponsor's geometric ratio is accompanied by a 90% confidence interval, but the acceptance limits and detailed method are not reported in the registry record. Without these, the interval cannot establish whether the registered bioequivalence criterion was satisfied. The record also does not report a sponsor p-value for that ratio analysis.

The primary population is described as study completers, but completion counts, withdrawal reasons, missing-data procedures, and sensitivity analyses are not reported. Three outcome measures and analyses are listed, but no secondary results are posted, and multiplicity handling is not described. These reporting gaps limit independent evaluation of the results and their robustness; they do not show that a specific bias or analytic problem occurred.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Mycophenolate Mofetil 250 mg Capsules Under Fasting Conditions — NCT00911274.
• Registry record last updated 2024-08-19; status last verified 2024-08.
• Results first posted 2009-09-23.
• 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

NCT00911274 is a completed Phase 1 randomized crossover study sponsored by Teva Pharmaceuticals USA. It compared a single dose of mycophenolate mofetil 250 mg capsules with CellCept® 250 mg capsules under fasting conditions in healthy subjects. The registry lists enrollment of 53 and describes two treatment sequences across two periods.

The primary endpoint was Cmax, with blood samples collected over a 72 hour period. Treatment summaries report mean Cmax values of 8.586 µg/mL for the test and 9.217 µg/mL for the reference. The sponsor-reported geometric test-to-reference ratio is 92.41, with a 90% confidence interval from 82.77 to 103.18.

The registry record does not report the sponsor's detailed statistical method or bioequivalence acceptance limits. The posted results therefore support a description of the estimates and their uncertainty, but not an independent formal determination against unreported criteria.