Cefprozil for Oral Suspension 250 mg/5 mL, Non-fasting: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cefprozil for Oral Suspension 250 mg/5 mL, Non-fasting (NCT00835354), a randomized phase 1 study. The primary outcome is Cmax (Maximum Observed Concentration).

2. Clinical Question

This is a pharmacokinetic comparison, not a study of clinical benefit or treatment of a health condition. Its population was described as healthy adults, and the study conditions were non-fasting. The registry record does not report further population details such as age or sex distribution. The central statistical question is therefore how closely the two formulations’ measured concentration summaries compare in this study population and how much uncertainty accompanies those estimates.

3. Trial Design

The study is listed as Phase 1, randomized, unmasked, and crossover. It compared cefprozil for oral suspension 250 mg/5 mL from Teva Pharmaceuticals USA with CEFZIL® for Oral Suspension 250 mg/5 mL from Bristol-Myers Squibb. The registry title specifies non-fasting conditions, and the brief description identifies healthy, non-smoking adults as the intended population. The study status is completed.

A crossover design means participants receive more than one treatment condition at different times, so comparisons can use measurements from the same participant under each condition. General: within-participant comparisons can account for stable differences between participants, but their analysis needs to reflect the paired structure. The registry record does not report the treatment sequence, period structure, washout, or details of the crossover analysis. Those elements should not be inferred from the design label alone.

The record lists 26 participants enrolled and a primary endpoint population described as all participants who completed the study and had their samples analyzed. The posted endpoint summaries contain 25 observations for each treatment. The record does not explain the relationship between the enrollment count and the endpoint counts, nor does it give a detailed participant disposition.

Blood samples were collected over a 12 hour period for the primary outcome. The registry record lists three outcome measures and three analyses, but the details available for this interpretation focus on the primary Cmax outcome and the reported comparison. The sponsor is Teva Pharmaceuticals USA. Both the study start and primary completion are recorded as 2004-05. Original protocol details, including the rationale for the planned enrollment, 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.

First Intervention

Reasons for not completing this period:

Washout of 7 Days

Second Intervention

Analysis population for the primary outcome, as defined in the registry: All participants that completed the study had their samples analyzed.

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 a 12 hour period..

The primary endpoint is Cmax, the maximum observed concentration measured from blood samples collected over a 12 hour period. Concentration describes the amount of drug measured in a sample; the maximum observed value captures the highest measured concentration during the stated sampling window. The registry record gives the endpoint unit as ng/mL and describes its summary as a mean with standard deviation.

Cmax is used in pharmacokinetic comparisons because it provides a direct summary of peak concentration after administration. In this study, the endpoint description says that bioequivalence was based on Cmax, and the stated objective was to compare relative bioavailability under non-fasting conditions. The registry also reports a test-to-reference geometric-mean ratio, which expresses the formulations’ relative concentrations on a ratio scale.

General: a concentration endpoint is a measured quantity, not by itself a measure of clinical benefit or harm. Its interpretation depends on the study question, the analysis scale, and any prespecified criteria for comparing formulations. The registry record does not report an equivalence margin or further endpoint decision criteria, so the available Cmax estimates can describe the observed comparison and its precision but cannot, on their own, establish a formal bioequivalence conclusion.

7. Results Posted in the Registry

• Cefprozil (Test): mean 4.37 versus 4.92 on control; difference -0.55 (95% CI -0.99 to -0.11), standardized effect d = -0.70; z-test p = 0.014.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean summarize?

The endpoint is a continuous measurement, and the registry lists its parameter as the mean. A mean summarizes the observed values by their arithmetic average. For the posted treatment summaries, the mean is 4.367 ng/mL for the test formulation and 4.915 ng/mL for the reference formulation. Each summary is accompanied by a standard deviation, which describes the spread of individual measurements around the mean. The registry record does not provide the individual observations, so the distribution of Cmax values cannot be assessed directly from these summary statistics alone.

What is the recalculated mean difference?

The unadjusted recalculation subtracts the reference mean from the test mean. The resulting estimate is -0.548, so its sign indicates a lower test mean on this scale. The calculation uses the posted means and dispersion summaries and is not the sponsor’s reported ratio analysis. It is a simple comparison based on the summaries rather than an adjustment for the crossover design or any other covariates.

How should the confidence interval and p-value be read?

A confidence interval describes a range of values compatible with the data under the assumptions of the method used. For the recalculated difference, the interval excludes zero, in the same direction as the negative point estimate. The corresponding unadjusted p-value is 0.014. General: a p-value measures how unusual data at least as inconsistent with a null hypothesis would be if that null hypothesis and the analysis assumptions held. It does not measure the probability that the null is true, the probability that the result is due to chance, or the clinical importance of the estimate.

The registry record does not report the method used for the sponsor analysis in the available result entry. It does report the ratio of test-to-reference geometric means multiplied by 100, its point estimate, and a 90% confidence interval. General: geometric means are commonly used for positive measurements analyzed on a logarithmic scale; ratios then express relative rather than absolute differences. The record does not provide enough detail to infer the transformation, model, or specific estimation method used by the sponsor.

Why does the crossover design matter?

In a crossover study, the same participant may contribute observations under both treatments. Those measurements are related because they come from the same person. A paired analysis uses that relationship, often improving the precision of a comparison when within-person measurements are correlated. General: treating paired measurements as independent can fail to represent the design and can misstate uncertainty. The unadjusted recalculation from the posted summaries cannot recover participant-level pairing, sequence, or period effects. The registry record does not report the sponsor’s method in enough detail to determine how these aspects were handled.

The posted summary statistics include a standardized effect estimate of -0.695 and pooled standard deviation information, but the recalculated mean difference remains the more direct expression of the absolute difference on the endpoint’s stated scale. A standardized effect expresses a difference relative to variability and can be useful for planning illustrations; it does not replace the measured difference in ng/mL. The registry record does not report the precise original analysis plan or whether the standardized quantity was part of it.

What is the sponsor’s ratio analysis?

The reported test-to-reference geometric-mean ratio multiplied by 100 is 89.2. Its 90% confidence interval runs from 86.2 to 92.2. General: ratio analyses are naturally interpreted against 100 when the ratio is multiplied by 100, because this represents equal geometric means. A confidence interval gives the range of relative values compatible with the analysis and data, subject to the method’s assumptions. To judge formal bioequivalence, the interval must be assessed against prespecified lower and upper limits. Those limits and the sponsor’s detailed decision rule are not reported in the registry record.

What does the record not establish about the analysis?

The registry record does not report the original statistical analysis plan, the model used for the reported ratio, a crossover-specific method, or whether an interim analysis was conducted. It also does not report a multiplicity procedure for the three listed outcome measures and analyses. Those omissions mean that the available summary cannot establish which model assumptions were checked, how any multiple comparisons were handled, or whether further analyses were prespecified. General: a statistical estimate is most interpretable when its analysis population, model, assumptions, and decision criteria are fully described.

10. Confidence Intervals and Precision

The sponsor-reported ratio estimate is 89.2, with a 90% confidence interval from 86.2 to 92.2. The interval represents uncertainty around the estimated relative geometric mean, under the sponsor analysis and its assumptions. It is centered around an estimate below 100, the ratio-scale value corresponding to equality. The interval communicates a range rather than a guarantee that the true value lies within those limits.

The recalculated difference is -0.548. Its confidence interval excludes zero, matching the negative direction of the point estimate. The interval is based on an unadjusted recalculation from posted summary statistics, not a reconstructed paired analysis of the crossover data. Its precision should therefore be interpreted with that limitation in mind. The registry record does not provide individual participant results or enough detail to reproduce the sponsor’s model.

Confidence intervals answer questions about statistical precision, not whether a difference is important or whether an equivalence criterion is satisfied. General: a narrower interval indicates less uncertainty under the chosen analysis, while a wider interval indicates more uncertainty. Whether a ratio interval supports a formal equivalence conclusion depends on the prespecified acceptable range. That range is not reported in the registry record, so the ratio interval cannot be assessed against formal limits from the available information.

The listed 25 observations for each treatment provide the basis for the endpoint summaries, but the precision of a crossover comparison also depends on the within-participant relationship. That relationship is not available in the posted aggregate statistics. The sponsor’s interval may use an analysis that accounts for the design, but its method is not reported in the registry result entry; no specific model should be assumed.

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 display is a planning illustration based on the observed effect, not the original trial’s design calculation. Its figures are participants per arm, not total events. The 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 set to the stated fraction of the observed effect. The original study’s sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the participants per arm estimated to yield an 80% chance of detecting the selected effect under those planning assumptions, if that effect is real and the assumptions hold. The 90% power column gives the corresponding per-arm planning estimate for a 90% chance. These are design calculations, not measurements of the probability that the completed trial found a true result. The figures are not observed power.

The display includes planning for 100%, 75%, and 50% of the observed effect. For example, planning for 75% of the observed effect gives 58 participants per arm for 80% power and 78 for 90% power. Planning for 50% of the observed effect gives 130 participants per arm for 80% power and 175 for 90% power. The corresponding figures for planning at 100% of the observed effect are 33 participants per arm for 80% power and 44 for 90% power.

The pattern illustrates a general relationship: smaller effects are harder to distinguish from random variation, so they require more participants under otherwise unchanged assumptions. A higher target power also requires a larger planned sample. These calculations use a two-arm, equal-allocation normal-approximation framework; the registry identifies the actual study as crossover. The planning illustration therefore should not be treated as a reconstruction of the trial’s original design or as a substitute for a crossover-specific calculation.

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 = -0.548; pooled standard deviation σ = 0.788.
2. n = 2 × (1.96 + 0.842)² × 0.788² / -0.548² = 32.5, rounded up to 33 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 <- -0.548                      # observed difference in means
sigma <- 0.788480183644459                     # 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(835354)
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 = 33 (80% power), 44 (90% power)
 75% of observed effect: n per arm = 58 (80% power), 78 (90% power)
 50% of observed effect: n per arm = 130 (80% power), 175 (90% power)
power.t.test: 33.5 
Simulated power at n = 33 per arm: 0.790 (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-reported analysis expresses the comparison as the test-to-reference geometric-mean ratio multiplied by 100. The estimate is 89.2, with a 90% confidence interval from 86.2 to 92.2. This is the registry’s own reported relative analysis. The method field is not reported, so the specific model and assumptions behind that result cannot be described in detail.

The separate recalculation uses the posted arithmetic means and estimates a test-minus-reference difference of -0.548, with an unadjusted p-value of 0.014. Its direction is consistent with a lower test mean, but it is not the same estimand as the sponsor’s ratio. The recalculation is unadjusted and does not use participant-level paired data from the crossover design. It therefore should not replace the sponsor-reported ratio result or be treated as an independent reproduction of the sponsor’s analysis.

The sponsor’s ratio estimate and its interval can be assessed for formal bioequivalence only with the study’s prespecified acceptance limits and decision rules. Those limits are not reported in the registry record. The registry does not report enough information to determine how the sponsor’s analysis addressed crossover structure, transformations, or other model choices. The sponsor result is best read as the reported relative estimate and uncertainty, with these reporting limits kept in view.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures and three analyses. The detailed result information discussed for this comparison concerns the primary Cmax endpoint. It does not describe a multiplicity adjustment, a hierarchy of outcomes, or a rule for interpreting several statistical tests together. Whether or how multiplicity was handled is not reported in the registry record.

General: when a study tests multiple outcomes or makes multiple comparisons, the chance of obtaining at least one apparently unusual result can increase if each test is interpreted separately. Statistical plans may address this through prespecified primary outcomes, testing sequences, or adjustments. The record identifies Cmax as the primary endpoint but does not provide enough information to establish the planned handling of all analyses or whether the reported p-value was adjusted.

The registry describes the primary analysis population as all participants who completed the study and had their samples analyzed. It lists 26 participants enrolled and treatment summaries with 25 observations each. A detailed flow of participants, reasons for non-completion, missing sample information, or exclusions is not reported in the registry record. The record therefore does not establish whether any data were missing, how missing measurements were handled, or whether all randomized participants were included in each analysis.

The study is identified as a crossover, but the reported summary statistics do not include the within-participant data needed to evaluate paired completeness or to reproduce a crossover analysis. The record does not describe treatment sequence, period effects, carryover assessment, or a model for repeated observations. These are relevant details for interpreting a crossover comparison, but they should not be inferred from the design label.

Interim analyses, stopping rules, and the original statistical analysis plan are not reported in the registry record. General: prespecified methods help distinguish planned analyses from choices made after results are known. Because the relevant documentation is not reported, the available results support a description of the posted estimates and their stated summaries, not a conclusion about every feature of the analysis process.

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

The posted results describe a difference in measured Cmax between the two formulations in a healthy, non-smoking adult population under non-fasting conditions. The test formulation has a lower posted mean than the reference formulation, and the recalculated unadjusted mean difference is negative. The sponsor-reported ratio also has an estimate below 100. Together, these statistics describe the relative concentration results in this study; they do not establish a clinical effect.

The sponsor’s 90% confidence interval gives uncertainty around the reported geometric-mean ratio. The registry record does not report the acceptable limits used to decide formal bioequivalence, so the estimate and interval cannot be used on their own to conclude that the study met a formal criterion. Likewise, the recalculated unadjusted p-value addresses a difference comparison and is not itself a bioequivalence decision rule.

General: statistical significance, precision, clinical importance, and equivalence are distinct ideas. A p-value can indicate how compatible the observed data are with a null hypothesis under an analysis, while an interval conveys uncertainty about an estimate. Clinical importance requires context beyond statistical evidence, and equivalence requires prespecified bounds and a suitable analysis. The available record does not report all of that context.

The findings are specific to the formulations, non-fasting conditions, sampling window, and population described. The registry record does not report results for other populations, conditions, or clinical outcomes. It also does not provide enough detail to generalize the concentration comparison beyond this study or to draw conclusions about treatment decisions. The results should be understood as pharmacokinetic estimates from the completed Phase 1 study, alongside the limitations of the reported analysis details.

16. Why This Trial Matters Statistically

This study raises a useful statistical distinction between absolute and relative comparisons. The unadjusted recalculation reports an arithmetic mean difference of -0.548, whereas the sponsor reports a test-to-reference geometric-mean ratio multiplied by 100. Both describe the treatment comparison, but they use different scales and should not be substituted for one another. Clear identification of the estimand and scale is essential when interpreting a formulation comparison.

The crossover design also makes analysis structure important. Because participants may contribute measurements under both formulations, the comparison is not simply a conventional parallel-group comparison. General: paired analysis can use within-person information, while a calculation from group-level summaries cannot recover that information. The unadjusted recalculation is informative as a simple summary-based contrast, but it does not account for participant pairing.

The sponsor-reported confidence interval gives a direct measure of uncertainty on the ratio scale, but a formal equivalence interpretation requires criteria that are not reported in the registry record. This illustrates why estimates and intervals should be read together with the decision rule a study set out to use. Without the bounds, the ratio can be described, but a formal pass-or-fail interpretation cannot be reconstructed.

Finally, the planning illustration shows how required sample size changes with the effect selected for detection and with the target power. It is not a reconstruction of the original study plan, and its assumptions differ from details needed to model a crossover design. Separating study findings from planning calculations helps prevent the observed estimate from being mistaken for a prospective design target.

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 original sample-size justification, detailed protocol, or statistical analysis plan. Consequently, the reason for the enrollment target, the prespecified model, and the decision criteria for bioequivalence cannot be assessed from the record. The planning illustration is based on the observed effect and should not be interpreted as the study’s original design calculation.

The study is labeled crossover, but treatment sequence, period structure, washout, and the handling of within-participant measurements are not reported. The sponsor analysis method is also not reported in the result entry. The unadjusted recalculation uses aggregate summaries and cannot account for participant pairing or other crossover features.

The record lists 26 enrolled participants and 25 observations for each treatment in the endpoint summaries, but it does not give a detailed participant disposition or explain the counts. It states that samples from participants who completed the study were analyzed. Reasons for non-completion, missing measurements, exclusions, and the handling of missing data are not reported in the registry record.

The reported result concerns Cmax measured during a 12 hour sampling period in healthy, non-smoking adults under non-fasting conditions. The available information does not establish how representative the sample is of other populations or conditions. The record also does not report an equivalence margin, detailed multiplicity procedures, or whether interim analyses occurred. These limits constrain interpretation to the posted estimates and the study description available in the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Cefprozil for Oral Suspension 250 mg/5 mL, Non-fasting — NCT00835354.
• Registry record last updated 2024-08-20; status last verified 2024-08.
• Results first posted 2009-07-21.
• 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

NCT00835354 is a completed Phase 1 randomized, unmasked crossover study sponsored by Teva Pharmaceuticals USA. It compared cefprozil for oral suspension 250 mg/5 mL with CEFZIL® for Oral Suspension 250 mg/5 mL in healthy, non-smoking adults under non-fasting conditions. The record lists 26 participants enrolled.

The primary endpoint was Cmax, measured from blood samples collected over a 12 hour period. The posted means were 4.367 ng/mL for the test formulation and 4.915 ng/mL for the reference, with 25 observations listed for each treatment. The sponsor reported a test-to-reference geometric-mean ratio of 89.2 and a 90% confidence interval from 86.2 to 92.2. The unadjusted recalculation estimates a mean difference of -0.548 and reports p = 0.014.

The registry record does not report the formal equivalence limits, detailed sponsor method, or original sample-size justification. The result is therefore best read as a Cmax comparison with the stated reporting and analysis limitations.