Ondansetron HCl Orally Disintegrating Tablets Under Fasting Conditions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ondansetron HCl Orally Disintegrating Tablets Under Fasting Conditions (NCT00934180), 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, unmasked crossover study sponsored by Teva Pharmaceuticals USA. Its official title describes a relative bioavailability study of Ondansetron HCl 8 mg orally disintegrating tablets under fasting conditions. The registry records the study as completed and enrollment as 24.

The two sequences reversed the order in which the formulations were received. One sequence received Ondansetron HCl 8 mg OD Tablet in the first period and Zofran® 8 mg ODT in the second period. The other received Zofran® 8 mg ODT first and Ondansetron HCl 8 mg OD Tablet second. Thus, each listed sequence included both formulations, with the assigned order differing. The registry identifies the model as crossover and allocation as randomized.

In a crossover design, participants serve as their own comparison across treatments. This can reduce the influence of stable differences between people when treatment responses are compared. The order of treatment and any possible period or carryover effects still matter to interpretation. The registry record does not report the washout interval, sequence-specific results, the method used to account for period or sequence, or whether carryover was assessed.

Masking is recorded as none. The record therefore does not describe blinded treatment assignment or outcome assessment. Although the intervention and sequence descriptions specify the formulations and their order, details such as dosing procedures, adherence, and the timing of doses beyond the stated periods are not reported in the registry record. The dates of study start and primary completion are recorded in the registry, but they are not needed to interpret the posted endpoint summaries.

The primary analysis population is described as data from all subjects who completed the study. Whether every enrolled participant completed both periods, and how any incomplete observations were handled, is not reported in the registry record. The record lists three outcome measures and three analyses, but no secondary outcomes are posted.

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.

First Intervention

Second Intervention

Analysis population for the primary outcome, as defined in the registry: Data from all subjects who completed the study were 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 24 hour period.

The primary endpoint was Cmax, or maximum observed concentration, measured in ng/mL. It represents the highest observed concentration of the measured drug in blood over the sampling period. The registry says blood samples were collected over a 24 hour period and describes the endpoint as bioequivalence based on Cmax.

As a general pharmacokinetic concept, Cmax is used to describe peak exposure after a dose. Comparing peak concentrations between formulations can contribute to a relative bioavailability assessment: it addresses whether the observed concentration profiles reach similar maximum levels. It is one aspect of exposure, not a complete description of the concentration-time profile. Other measures may address total exposure or the timing of the peak, but the posted primary endpoint is Cmax.

The registry's group summaries report means and standard deviations for the two formulations. The sponsor's analysis is presented as a ratio of geometric means, while the recalculation uses the posted arithmetic means to give an unadjusted mean difference. These are different summaries and should not be treated as interchangeable. The registry record does not report details of the concentration assay, the sampling schedule within the stated period, or a rationale for selecting Cmax as the primary endpoint beyond the description that the analysis concerns bioequivalence.

7. Results Posted in the Registry

• Zofran®: mean 31.75 versus 32.10 on control; difference -0.34 (95% CI -11.37 to 10.68), standardized effect d = -0.02; z-test p = 0.951.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover design compare?

In a crossover study, the same participant receives more than one treatment, usually in a planned order. Each participant can then contribute observations under both treatments, allowing a within-participant comparison. This can help control stable participant characteristics that would otherwise contribute to differences between separate treatment groups.

Order still matters. Concentrations can differ by period, and effects from an earlier treatment can potentially persist into a later period. Randomizing treatment order can help distribute order-related influences, but it does not by itself demonstrate that period or carryover effects were absent. The registry identifies a randomized crossover model and gives the two treatment sequences. It does not report a washout interval, an assessment of carryover, a period or sequence analysis, or the statistical model used for the sponsor's result.

What is the difference between a mean difference and a ratio?

The posted arm summaries give arithmetic means for Cmax. The unadjusted recalculation expresses the comparison as a mean difference: the Ondansetron mean relative to the Zofran® mean on the ng/mL scale. Its estimate is -0.343, with a 95% confidence interval from -11.37 to 10.68. A difference is expressed in the original measurement units.

The sponsor's posted analysis is expressed as a ratio of geometric means, reported as 103 with a 90% confidence interval from 95.1 to 111. A ratio compares values on a relative scale rather than subtracting them on the original scale. Arithmetic and geometric means summarize data differently, and a ratio is not the same estimand as an arithmetic mean difference. The registry does not report the sponsor's method, so the transformation and model behind that result are not described in the record.

As a general statistical concept, geometric summaries are often used for measurements with distributions that are skewed or analyzed on a logarithmic scale. That general rationale does not establish that a particular model or transformation was used in this study. The record identifies the sponsor's parameter as a ratio of geometric means but does not report its calculation details.

What does the unadjusted recalculation represent?

The recalculated comparison uses the posted group means and standard deviations to describe an unadjusted difference. It is useful as a transparent comparison of the published summary statistics, but it does not use the participant-level paired measurements that are ordinarily important to a crossover analysis. The posted estimate, interval, and p-value should therefore be read as a summary-statistic recalculation, not as a reconstruction of the sponsor's analysis.

The recalculated interval is a confidence interval for the estimated difference under the assumptions of that calculation. A confidence interval describes uncertainty in an estimate; it does not give the probability that the true value lies in the particular interval. Its width reflects both the variability in the observations and the amount of information available for the analysis. The posted standard deviations show variability within each arm, but the within-participant correlation is not reported. Without that correlation, an independent summary-statistic calculation cannot fully represent the paired structure.

The unadjusted p-value is 0.951. It is a test statistic summary under the assumptions of the recalculation, not a measure of effect size, clinical importance, or the probability that the null hypothesis is correct. The interval and p-value answer related questions about evidence for a difference, but neither resolves whether the formulations meet an equivalence criterion.

What does a bioequivalence analysis require?

As a general concept, a bioequivalence analysis typically evaluates whether a confidence interval for a relative measure falls within predefined acceptance limits. The choice of measure, transformation, confidence level, and acceptance limits are features of the analysis plan. The registry reports the geometric-mean ratio and its 90% confidence interval, but the acceptance limits and statistical method are not reported in the registry record. Without those limits and method details, the ratio interval alone does not show whether the sponsor's formal criterion was met.

The registry describes the primary endpoint as bioequivalence based on Cmax, but the available record does not explain the full decision rule. No equivalence margins should be inferred from the reported interval or from customary practice. The sponsor's analysis remains the relevant posted analysis for its stated objective, while the recalculation provides a distinct unadjusted view of the posted arithmetic summaries.

More generally, estimates, confidence intervals, and decision criteria serve different roles. An estimate gives the central value from an analysis; an interval conveys uncertainty around that estimate; and a predefined criterion specifies how the evidence is to be judged for a particular question. The record supplies an estimate and interval for the sponsor's ratio, but not its criterion. This distinction is important when reading a relative bioavailability study: a numerical ratio near a reference value does not by itself establish a formal equivalence conclusion.

10. Confidence Intervals and Precision

The unadjusted mean-difference estimate is -0.343 ng/mL, with a 95% confidence interval from -11.37 to 10.68. Because the interval spans zero and includes values on either side, the recalculation is compatible with either direction of difference. Its breadth means that the estimate is not precise enough to pin down a narrow range of mean differences on the original scale.

A confidence interval is a range of values that, under the analysis assumptions, is consistent with the observed data at the stated confidence level. In repeated use of the same procedure, intervals constructed in this way would cover the target value at the stated rate. It is not correct to interpret a particular interval as assigning a probability to the true value after the data have been observed.

The sponsor's reported ratio of geometric means is 103, with a 90% confidence interval from 95.1 to 111. That interval communicates uncertainty on the ratio scale and uses a different confidence level from the 95% interval for the unadjusted arithmetic mean difference. These intervals are not directly comparable as though they estimated the same quantity. The registry does not report the sponsor's model or the criteria against which its interval was judged.

Precision is affected by variability, the amount of information, and the analysis design. The arm standard deviations are 18.67 for Ondansetron and 20.27 for Zofran®. In a crossover analysis, the variability of within-participant differences is also relevant, but that information is not reported in the registry record. The enrollment and arm summaries alone do not reveal the precision of a paired estimate or explain the sponsor's interval.

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, not a reconstruction of the trial's original design. For this continuous outcome, the entries represent participants per arm, not total events. The table varies the effect assumed for planning: 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Within each effect assumption, the columns give participants per arm for 80% power and participants per arm for 90% power.

In plain language, 80% power describes a planning target in which a study using the stated assumptions would have an 80% chance of detecting the specified effect at the stated significance level. The 90% power column uses a higher chance-of-detection target. Both are hypothetical planning quantities, not outcomes observed in this study. The posted 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.

Smaller effects require more participants to distinguish them from random variation under otherwise similar assumptions. That is why the planning illustration increases the assumed sample requirement as the target effect becomes a smaller fraction of the observed effect. The observed effect is small in the unadjusted recalculation, so planning from that estimate produces large illustrative requirements. Those figures should not be read as the enrollment target used by the sponsor: the original trial design assumptions are not reported in the registry record.

This is not observed power. It is a set of planning scenarios based on the observed effect and stated assumptions, and it does not alter the interpretation of the study's confidence intervals or p-value.

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 = -0.343; pooled standard deviation σ = 19.487.
2. n = 2 × (1.96 + 0.842)² × 19.487² / -0.343² = 50,666.3, rounded up to 50,667 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 <- -0.342999999999996                      # observed difference in means
sigma <- 19.4865520038821                     # 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(934180)
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 = 50,667 (80% power), 67,828 (90% power)
 75% of observed effect: n per arm = 90,074 (80% power), 120,583 (90% power)
 50% of observed effect: n per arm = 202,666 (80% power), 271,312 (90% power)
power.t.test: 50667.3 
Simulated power at n = 50,667 per arm: 0.797 (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 analysis reports a ratio of geometric means of 103, with a 90% confidence interval from 95.1 to 111. The recalculation from the posted arm summaries instead reports an unadjusted arithmetic mean difference of -0.343 ng/mL, with a 95% confidence interval from -11.37 to 10.68 and an unadjusted p-value of 0.951. These results are on different scales and use different summaries; they should not be expected to match numerically.

The recalculation is a simple unadjusted re-analysis of the posted means and standard deviations. It does not reproduce the sponsor's crossover analysis, whose method is not reported in the registry record. In particular, the record does not provide participant-level paired data or details of how the sponsor handled the crossover structure. The sponsor's analysis is the registry's reported analysis for the relative bioavailability question, while the recalculation is a supplementary descriptive comparison.

The registry record does not report the acceptance limits or full decision rule for the sponsor's analysis. Thus, the sponsor's ratio and confidence interval can be described, but the record does not allow independent confirmation of a formal bioequivalence decision from those values alone. The discrepancy flag is false, so no disagreement between the reported and recalculated analyses is flagged.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses, but no secondary outcomes are posted. The primary endpoint is identified as Cmax, and one sponsor analysis is reported for a ratio of geometric means. The record does not explain how the three analyses relate to each other, whether they were separate endpoints or analysis variants, or whether any multiplicity adjustment was planned or applied.

Multiplicity is a general concern when several outcomes, comparisons, or analyses are considered. Each additional test can create more opportunity for a chance finding, and statistical plans sometimes address this by controlling the overall error rate or by identifying a primary comparison in advance. The registry record does not report a multiplicity procedure, a hierarchy of endpoints, or whether the sponsor's result was selected from a broader set of analyses. No adjustment should be assumed.

The primary analysis population is described as data from all subjects who completed the study. The registry does not report the number completing both periods, exclusions from the analysis, or reasons for missing observations. It also does not explain how incomplete concentration profiles or missing measurements were handled. Because the study is a crossover, missing data in one period could affect a participant's ability to contribute a paired comparison; the record does not specify how that situation was addressed.

Other analysis-population definitions are not reported in the registry record. The available information does not identify an intention-to-treat population, a per-protocol population, or rules for deviations from assigned treatment. It also does not report sensitivity analyses for missing data or protocol deviations. These omissions limit the ability to assess the robustness of the sponsor's result and to determine exactly which participants contributed to each analysis.

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

The registry record describes a randomized, unmasked crossover comparison of two ondansetron formulations under fasting conditions in healthy, non-smoking adults. The primary outcome was maximum observed concentration over a 24 hour blood-sampling period. The posted arithmetic means are 32.1 ng/mL for Ondansetron and 31.75 ng/mL for Zofran®, and the unadjusted recalculation gives a mean difference of -0.343 ng/mL.

The recalculated 95% confidence interval, from -11.37 to 10.68, includes zero and spans a range of differences in both directions. The unadjusted p-value is 0.951. These statistics describe the uncertainty and test result for that recalculation; they do not prove that the formulations are identical. Nor do they establish that one formulation produces a clinically meaningful advantage over the other.

The sponsor's analysis reports a ratio of geometric means of 103 and a 90% confidence interval from 95.1 to 111. The record does not state the acceptance limits or full analysis method needed to assess a formal bioequivalence decision. Accordingly, the reported ratio and interval should be read as the sponsor's posted result, not as a sufficient basis for independently declaring equivalence from the registry record.

The data address a pharmacokinetic endpoint in the study population and fasting setting described. They do not answer questions about clinical outcomes, other patient populations, other dosing conditions, or unposted endpoints. Cmax is a measure of peak observed concentration, not a direct measure of benefit or harm. The registry record does not report adverse-event results in the information available for this analysis.

Overall, the posted statistics allow a careful description of the observed Cmax summaries and the uncertainty in the unadjusted comparison. They do not resolve all design and analysis questions, particularly the sponsor's crossover model, missing-data handling, and equivalence criteria. Those details are not reported in the registry record.

16. Why This Trial Matters Statistically

This study illustrates why the analysis scale and design matter when interpreting relative bioavailability results. The arm summaries are arithmetic means and standard deviations, while the sponsor's posted result is a ratio of geometric means. A simple unadjusted difference based on group summaries is informative as a descriptive check, but it is not a substitute for the sponsor's crossover analysis.

The crossover arrangement is also statistically important. Since participants received both formulations in different orders, their paired responses could be relevant to the precision of the treatment comparison. The posted arm summaries do not reveal the within-participant relationship between measurements. Without participant-level data or a detailed model description, the unadjusted recalculation cannot account for all features of the design.

The record also demonstrates the distinction between an estimate and a decision criterion. The sponsor reports a geometric-mean ratio and confidence interval, but the registry does not report the acceptance limits or full statistical plan. A confidence interval is useful for understanding precision, yet formal equivalence assessment depends on criteria that are not included in the record.

Finally, the planning illustration shows how sample-size requirements depend on the effect assumed for planning. It is not evidence about the trial's original sample-size rationale or a measure of the probability that this completed study detected an effect. Reading that illustration separately from the observed results helps prevent a planning scenario from being mistaken for a trial outcome.

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 does not report the sponsor's statistical method, including whether the crossover structure was modeled through within-participant comparisons or how period and sequence were handled. It also does not report a washout interval or an assessment of carryover. These details are relevant to interpreting a two-period treatment comparison.

The primary analysis population is described as subjects who completed the study, but the number completing both periods and the handling of withdrawals or incomplete observations are not reported in the registry record. Missing-data methods and protocol-deviation rules are also not reported. This limits assessment of which observations contributed to the primary analysis.

The sponsor's ratio of geometric means is accompanied by a 90% confidence interval, but the registry record does not provide the statistical model, transformation details, or acceptance limits for a formal equivalence assessment. The unadjusted recalculation uses posted group summaries and does not incorporate participant-level pairing. Its estimate and interval therefore should not be taken as a reproduction of the sponsor's analysis.

The study's stated population is healthy, non-smoking adults, and the comparison was conducted under fasting conditions. The registry record does not support extending the endpoint findings to other populations or conditions. No secondary outcome results are posted, and adverse-event findings are not part of the registry entries available for this analysis.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Ondansetron HCl Orally Disintegrating Tablets Under Fasting Conditions — NCT00934180.
• Registry record last updated 2024-08-21; status last verified 2024-08.
• Results first posted 2009-08-25.
• 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.

21. Record Summary

This completed Phase 1 study was randomized, unmasked, and crossover in design. Teva Pharmaceuticals USA sponsored the comparison of Ondansetron HCl 8 mg OD Tablet with Zofran® 8 mg ODT under fasting conditions in healthy, non-smoking adults.

The primary endpoint was Cmax in ng/mL, with blood samples collected over a 24 hour period. The posted means were 32.1 for Ondansetron and 31.75 for Zofran®. The unadjusted recalculation gave a mean difference of -0.343, a 95% confidence interval from -11.37 to 10.68, and an unadjusted p-value of 0.951. The sponsor reported a ratio of geometric means of 103 with a 90% confidence interval from 95.1 to 111.

The record does not report the sponsor's statistical method, equivalence limits, or details of missing-data handling. No secondary outcome results are posted.