Pantoprazole Sodium 40 mg DR Tablets Under Fasting Conditions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pantoprazole Sodium 40 mg DR Tablets Under Fasting Conditions (NCT00835588), a randomized phase 1 study. The primary outcome is Cmax - Maximum Observed Concentration - Pantoprazole in Plasma.

2. Clinical Question

3. Trial Design

This was a Phase 1 randomized crossover study sponsored by Teva Pharmaceuticals USA. Its title identifies the comparison as taking place under fasting conditions. The registry lists 100 participants enrolled, healthy subjects as the study population, and a completed status. The recorded start and primary completion are both 2003-12.

The two sequences reversed the order of the products. One sequence received pantoprazole sodium 40 mg delayed-release tablets first and PROTONIX® 40 mg delayed-release tablets second; the other received the reference product first and the test product second. In a crossover design, participants receive both treatments in separate periods, so treatment comparisons can use within-participant information. This differs from a design in which separate groups receive only one treatment. The registry record does not report the period duration, washout interval, or sequence-generation details beyond randomized allocation.

Masking is recorded as none. The registry record does not describe whether other study personnel were masked. The primary outcome analysis population is described as all subjects who completed the study. Each treatment-sequence outcome entry lists 100 participants, while total enrollment is also listed as 100. Those entries are consistent with repeated treatment-period information in a crossover record; they do not establish that 200 separate people took part.

The registry lists three outcome measures and three analyses. The primary endpoint is Cmax, the maximum observed plasma concentration. The record identifies the primary endpoint timeframe as blood samples collected over 16 hour period. It does not report the full protocol, the original sample-size justification, or the detailed statistical plan.

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

Washout: 5 Days

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 - Pantoprazole in Plasma, measured over Blood samples collected over 16 hour period.

The primary endpoint, Cmax, is the maximum concentration of pantoprazole observed in plasma over the sampling period. It is a continuous measure, recorded in ng/mL. The registry describes blood collection over 16 hour period and identifies bioequivalence based on Cmax as the endpoint description.

In general, a maximum concentration can characterize the peak exposure observed after administration. Comparing this measure between formulations is one way to examine relative bioavailability. Because the trial used a crossover design, participants received both products in different periods, allowing a comparison that may account for stable differences between individuals. The registry record does not explain how its sponsor analysis modeled the crossover structure or how it handled period or sequence effects.

The posted treatment-sequence summaries give arithmetic means and standard deviations: 2494 ng/mL with a standard deviation of 965 for the Pantoprazole sequence, and 2747 ng/mL with a standard deviation of 879.9 for the Protonix® sequence. These summaries are not themselves the sponsor’s reported geometric ratio analysis. The record also reports a geometric test-to-reference ratio multiplied by 100, with a 90% confidence interval. The specific transformation, model, and decision margin for that analysis are not reported in the registry record.

Cmax is one measure of exposure, not a complete description of every aspect of drug concentration over time. The registry lists other outcome measures but does not post secondary results in the record.

7. Results Posted in the Registry

• Protonix®: mean 2,747 versus 2,494 on control; difference 253.26 (95% CI -2.71 to 509.23), standardized effect d = 0.27; z-test p = 0.052.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the reported ratio represent?

The sponsor-reported endpoint analysis is expressed as a geometric test-to-reference ratio multiplied by 100. The reported value is 88.8, and its 90% confidence interval runs from 82.7 to 95.4. A ratio puts the comparison on a relative scale: it relates the test product’s endpoint to the reference product’s endpoint rather than subtracting one concentration from the other. Multiplication by 100 expresses the ratio on a percentage scale. The registry record does not describe the transformation or model used to obtain it, so those details cannot be reconstructed from the result alone.

In general, concentration measures may be analyzed on a transformed scale when the statistical method is based on relative comparisons. The transformation and the model matter because they determine how observations, periods, and participants contribute to the estimate and its uncertainty. The record does not report whether the sponsor modeled participant, treatment, period, or sequence effects, or whether another approach was used.

What is the recalculated mean difference?

The recalculated comparison uses the posted arithmetic means and standard deviations. It reports an unadjusted mean difference of 253.3, an interval from -2.706 to 509.2, and an unadjusted p-value of 0.052. These calculations are based on the posted group summaries and do not use the individual crossover pairing. They are not the sponsor’s reported ratio analysis.

In general, an unadjusted comparison is one that does not incorporate additional adjustment terms or design features beyond the calculation itself. Here, the key limitation is that the posted outcome entries are organized by sequence in a crossover study. Participants in the two sequences received both products, and their paired observations can carry information that is absent from separate group means and standard deviations. A summary-based independent-groups recalculation cannot recover that within-participant relationship.

The record gives a pooled standard deviation of 923.5 and a standardized effect of 0.274 for the recalculated comparison. These quantities describe the calculation attached to the posted summaries; they are not sponsor-reported crossover estimates. The registry record does not report a method for reconciling the arithmetic summaries with the geometric ratio result.

How should a p-value be read?

In general, a p-value measures how unusual data at least as inconsistent with a specified null hypothesis would be if that null hypothesis and the analysis assumptions were true. It is not the probability that the null hypothesis is true, nor is it a measure of clinical importance. The unadjusted recalculated p-value is 0.052. It pertains only to that simple recalculation and does not establish the result of the sponsor’s analysis.

For the sponsor result, the registry record reports no p-value. It also does not identify the precise hypothesis test, decision rule, or significance threshold used in the sponsor analysis. A p-value should not be inferred from the confidence interval or from the separate recalculation.

Why does the crossover design matter?

In general, crossover designs compare treatments within the same participants across periods. This can reduce the influence of stable between-person differences when the analysis uses paired information appropriately. It also requires attention to features such as period, sequence, and the interval between treatments. The registry record identifies the crossover model and the two treatment orders, but does not report the details of the sponsor’s statistical handling of these features or the washout interval.

The posted summaries list 100 observations for each sequence and the overall enrollment as 100. Because the sequences are treatment orders rather than separate groups that each received only one product, the sequence counts should not be interpreted as independent treatment-arm sample sizes. The primary endpoint population is described as subjects who completed the study.

What does the interval communicate?

In general, a confidence interval reflects the uncertainty around an estimate under a specified method. A wider interval indicates less precision than a narrower interval on the same scale, while the endpoints show the range of estimates compatible with that analysis and confidence level. The sponsor’s interval is reported at 90%; the recalculated interval has no confidence level stated in the registry record. Neither interval identifies the complete set of assumptions behind its calculation.

For a bioequivalence interpretation, the estimate and interval need to be considered against prespecified acceptance limits. The registry record does not report those limits. It also does not report the original sample-size justification, interim analyses, or a detailed statistical analysis plan. Consequently, the available results permit explanation of the reported quantities, but not reconstruction of every design or analysis decision.

10. Confidence Intervals and Precision

The sponsor analysis reports a geometric test-to-reference ratio multiplied by 100 of 88.8. Its 90% confidence interval extends from 82.7 to 95.4. This interval conveys uncertainty around the ratio estimate under the sponsor’s analysis. The registry record does not report the model or other analysis details needed to reproduce the interval, and it does not give the prespecified acceptance bounds needed to interpret it as a formal bioequivalence decision.

The recalculated arithmetic mean difference is 253.3, with an interval from -2.706 to 509.2. The registry record does not state the confidence level for this recalculated interval. It is based on summary statistics and does not incorporate the paired structure of the crossover design. It should not be used as if it were the sponsor’s interval or as if it answered the same relative-comparison question.

In general, an interval’s precision depends on both the amount of information and the variability in the data, as well as the analysis method. For a crossover study, within-participant variability can be important; the posted group summaries do not show the correlation between each participant’s observations under the two products. That missing information limits what can be learned about the precision of a paired treatment contrast from these summaries.

The standard deviations reported for the two sequence summaries are 965 and 879.9. They describe spread in the posted endpoint summaries, but they do not replace a treatment-effect interval. The sponsor ratio and the recalculated difference use different scales and analyses, so their interval widths cannot be compared as though they represented the same estimand.

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 events. They are illustrations based on the observed effect, not the original trial design. The assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect. The trial’s own sample-size assumptions and original justification are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm under which the planning calculation would have an 80% chance of detecting the specified effect, assuming the calculation’s assumptions hold. The 90% power column gives the corresponding number per arm for a 90% chance. These are design-planning concepts, not guarantees about what a future study would find. The values do not describe the observed power of this completed trial.

For planning for 100% of the observed effect, the figures are 209 participants per arm for 80% power and 280 participants per arm for 90% power. For planning for 75% of the observed effect, they are 372 and 497 participants per arm. For planning for 50% of the observed effect, they are 835 and 1,118 participants per arm.

In general, smaller effects are harder to distinguish from random variation, so detecting smaller effects with the same target power requires more participants. The illustrations use the observed effect as their starting point, which does not mean that effect is the true or clinically important target. The calculations are not the trial’s own design rationale and should not be read as evidence that the completed study had a particular probability of success.

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 = 253.260; pooled standard deviation σ = 923.462.
2. n = 2 × (1.96 + 0.842)² × 923.462² / 253.260² = 208.7, rounded up to 209 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 <- 253.26                      # observed difference in means
sigma <- 923.462339201767                     # 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(835588)
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 = 209 (80% power), 280 (90% power)
 75% of observed effect: n per arm = 372 (80% power), 497 (90% power)
 50% of observed effect: n per arm = 835 (80% power), 1,118 (90% power)
power.t.test: 209.7 
Simulated power at n = 209 per arm: 0.806 (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 result is a geometric test-to-reference ratio multiplied by 100 of 88.8, with a 90% confidence interval from 82.7 to 95.4. It is the posted result for the sponsor’s analysis of the primary endpoint. The registry record does not report its model, a sponsor-reported p-value, or the acceptance bounds used for any formal bioequivalence decision.

The recalculated result is an unadjusted arithmetic mean difference of 253.3, with an interval from -2.706 to 509.2 and an unadjusted p-value of 0.052. It is calculated from posted group summaries, without the paired participant-level information from the crossover. A difference on the arithmetic scale is not the same estimand as a geometric ratio on a relative scale; the estimates should not be treated as competing versions of one calculation.

The record does not flag a discrepancy. That status does not establish that the methods are interchangeable or that the recalculation reproduces the sponsor analysis. The sponsor’s reported result and the recalculation answer different statistical questions with different information. The sponsor result should be described as the sponsor’s analysis, while the summary-based calculation should be kept clearly labeled as an unadjusted recalculation.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses. It identifies Cmax as the primary endpoint, while the record posts no secondary results. The registry record does not describe a multiplicity adjustment, a hierarchy among endpoints, or any rule for interpreting several outcome tests together. It is therefore not possible to determine whether multiplicity was addressed in the original statistical plan or how it would affect the interpretation of all planned outcomes.

In general, testing several outcomes or hypotheses can increase the chance of at least one apparently notable result arising by chance. Methods such as prespecified testing hierarchies or adjusted significance thresholds can address that issue, but the record does not say whether any such method was used. No additional adjustment should be assumed from the fact that one endpoint is labeled primary.

The primary analysis population is described as all subjects who completed the study. The record does not report how many enrolled subjects completed both periods, whether any participants withdrew, or how incomplete treatment periods were handled. Although each treatment-sequence outcome entry lists 100 participants and total enrollment is 100, the record does not provide a participant flow accounting that explains these counts.

The registry record also does not report how missing blood samples, values below or above assay limits, protocol deviations, or other incomplete endpoint data were handled. It does not describe imputation, exclusions beyond the completer population statement, or sensitivity analyses. These omissions limit assessment of whether missingness or exclusions could have affected the estimate.

The record identifies randomization, no masking, and a crossover model, but does not report allocation procedures, the analysis model, or the treatment of period and sequence effects. It also does not report interim analyses or the original statistical analysis plan. These details should be treated as unreported in the registry record, rather than inferred from standard practice.

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

The posted results describe Cmax in healthy subjects under fasting conditions and compare a test pantoprazole product with a reference product in a randomized crossover study. The sponsor reports a geometric test-to-reference ratio multiplied by 100 of 88.8, with a 90% confidence interval from 82.7 to 95.4. These figures summarize the reported relative comparison and its uncertainty under the sponsor’s analysis.

The record does not report the acceptance bounds or full analysis method needed to determine whether the sponsor result met a predefined bioequivalence criterion. A ratio and confidence interval are not, by themselves, a complete decision rule. The registry record therefore supports reporting the estimate, interval, and study context, but not declaring that a formal criterion was satisfied or failed.

The arithmetic summaries show mean Cmax values of 2494 ng/mL and 2747 ng/mL for the two treatment sequences. The separate unadjusted recalculation gives a mean difference of 253.3 and p-value of 0.052. Because this calculation does not use crossover pairing and is on a different scale from the sponsor’s ratio analysis, it does not establish or refute the sponsor result.

The results apply to the recorded study setting: healthy, adult, non-smoking subjects studied under fasting conditions. They do not directly describe other populations or conditions not represented in the registry record. The outcome is a concentration measure collected over a 16 hour period, not a report of every possible pharmacokinetic feature or a clinical outcome.

These statistics are descriptions of a study and its analyses, not medical advice. They do not establish an individual response, a treatment recommendation, or results outside the measured endpoint and study population. The registry record does not provide enough detail to reconstruct the complete protocol or every analysis decision.

16. Why This Trial Matters Statistically

This study illustrates why the design and scale of an analysis matter when interpreting a result. A crossover trial gives each participant both products in different periods, so within-person comparisons can contain information that separate sequence means and standard deviations do not preserve. A calculation that treats those summaries as independent groups cannot reproduce a paired analysis.

It also shows why different statistical summaries should not be conflated. The sponsor reports a geometric ratio, which describes a relative comparison, while the recalculation reports an arithmetic mean difference. Both can be useful descriptions, but they address different scales and depend on different analysis choices. Their values and intervals are not direct substitutes.

Precision and decision criteria are also distinct. A confidence interval describes uncertainty in an estimate, but a decision about bioequivalence depends on prespecified limits and an appropriate analysis. The registry record reports a 90% interval for the sponsor ratio but not the acceptance limits or full statistical model. Without those details, the result can be described accurately without claiming a formal decision.

Finally, the sample-size illustrations demonstrate how planning depends on the effect one aims to detect and the desired power. They are planning scenarios based on the observed effect, not a reconstruction of the original design rationale and not observed power. Taken together, these features make the record useful for teaching careful interpretation: distinguish design from analysis, an estimate from a decision, and an illustrative recalculation from the sponsor’s reported result.

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 leaves important design and analysis details unreported. It does not give the original sample-size justification, detailed statistical analysis plan, or interim analysis information. The sponsor’s model for the crossover comparison, including its handling of participant, period, and sequence effects, is not described. The washout interval and treatment-period details are also not reported.

The primary analysis population is described as participants who completed the study, but the record does not give a participant flow account or explain the handling of incomplete periods and missing blood samples. This makes it difficult to assess whether the completer population differs from all enrolled participants. The entries list 100 observations for each sequence as well as total enrollment of 100, without explaining the counts in a flow diagram or narrative.

The study population was healthy, adult, and non-smoking, and the comparison took place under fasting conditions. The findings therefore have a specific setting and population; the registry does not establish how they generalize to other groups or conditions. Blood sampling is described over 16 hour period, but the record does not give further timing details.

The sponsor’s reported ratio and 90% confidence interval are posted without the equivalence margins or statistical method needed to reconstruct the decision process. The arithmetic mean comparison is a separate unadjusted recalculation from group summaries and lacks the paired data needed to account for the crossover design. No secondary results are posted, despite the listing of three outcome measures and three analyses. These record-level limitations constrain interpretation without implying that unreported procedures were or were not used.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Pantoprazole Sodium 40 mg DR Tablets Under Fasting Conditions — NCT00835588.
• Registry record last updated 2024-08-20; status last verified 2024-08.
• Results first posted 2009-08-18.
• 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

NCT00835588 was a completed, randomized, unmasked Phase 1 crossover study sponsored by Teva Pharmaceuticals USA. It enrolled 100 healthy subjects and compared pantoprazole sodium 40 mg delayed-release tablets with PROTONIX® 40 mg delayed-release tablets under fasting conditions. The two sequences received the products in opposite orders.

The primary endpoint was maximum observed pantoprazole concentration in plasma, measured in ng/mL from blood samples collected over 16 hour period. The sponsor-reported geometric test-to-reference ratio multiplied by 100 was 88.8, with a 90% confidence interval from 82.7 to 95.4. A separate unadjusted recalculation from posted summaries gives a mean difference of 253.3, an interval from -2.706 to 509.2, and p = 0.052; it does not use crossover pairing.

The registry record does not report the sponsor model, equivalence limits, original sample-size justification, or detailed handling of missing data. No secondary results are posted.